1887

Chapter 5 : Cellular Immune Responses to Xenografts

Author: Ronald G. Gill1
VIEW AFFILIATIONS HIDE AFFILIATIONS
Affiliations: 1: Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver, CO 80262
Content Type: Monograph
Publication Year: 2001

Category: Immunology

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Preview Magnify
Zoom in
Zoomout

Cellular Immune Responses to Xenografts, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555818043/9781555811679_Chap05-1.gif /docserver/preview/fulltext/10.1128/9781555818043/9781555811679_Chap05-2.gif

Abstract:

This chapter centers on adaptive or antigen-specific cellular responses to xenografts. It emphasizes the nature of T-lymphocyte-dependent immunity to xenografts. Most of the concepts concerning T-cell responses to xenografts developed in the chapter are derived from rodent studies. When considering the T-lymphocyte response to non-self antigens, including xenografts, it is imperative to emphasize the two fundamental properties of T-cell reactions. Although transferred human cells can mediate the rejection of human allografts or porcine xenografts in these animals, they generally fail to initiate vigorous GVHD against the scid mouse host itself. This model of donor MHC-restricted (direct) and host MHC-restricted (indirect) pathways of graft antigen presentation has important implications for the nature of T-cell-dependent immune responses to both allografts and xenografts. Two differing pathways of graft antigen presentation can be envisioned that would fulfill the two-signal requirement for T-cell activation, each involving APC-dependent processes: (i) donor MHC-restricted responses, and (ii) host MHC-restricted responses. CD4-dependent xenograft rejection depends on host and not on donor MHC class II expression. We find that CD4 T cells trigger rapid rejection of rat islet xenografts established in immunodeficient recombinase-activating gene (rag)-deficient hosts. Immunodeficient scid and -deficient mice accept tissue and organ xenografts despite retaining innate immune reactivity, including NK-cell function. The precise molecular mechanisms of cellular xenograft rejection remain to be identified, especially regarding the role of particular Th1 and Th2 cytokines in triggering tissue injury.

Citation: Gill R. 2001. Cellular Immune Responses to Xenografts, p 99-115. In Platt J (ed), Xenotransplantation. ASM Press, Washington, DC. doi: 10.1128/9781555818043.ch5

Key Concept Ranking

MHC Class II
0.8455401
MHC Class I
0.79303485
Innate Immune System
0.7812018
Major Histocompatibility Complex
0.6356518
0.8455401
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Cellular Immune Responses to Xenografts
[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555818043.chap5-1,webId=/content/author/10.1128/9781555818043.chap5-1,properties={foaf_givenname=Ronald G., foaf_name=Ronald G. Gill, foaf_surname=Gill, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555818043.chap5-aff1]]}]]
Citation: Gill R. 2001. Cellular Immune Responses to Xenografts, p 99-115. In Platt J (ed), Xenotransplantation. ASM Press, Washington, DC. doi: 10.1128/9781555818043.ch5
/content/10.1128/9781555818043.chap5.fig5-1
Figure 1

Direct and indirect pathways of graft antigen presentation. Optimal T-lymphocyte activation requires T-cell receptor recognition of processed peptide antigens complexed with MHC molecules plus appropriate secondary costimulatory signals provided by the antigen-presenting cell (APC). Four potential scenarios are depicted whereby CD4 or CD8 T cells can be activated in response to graft-derived antigens: (1) Direct (donor MHC-restricted) CD4 T-cell activation. In this case, the donor-type APC directly presents its own repertoire of peptides associated with MHC class II molecules to specific CD4 T cells. (2) Direct CD8 T-cell activation. Donor APCs directly present MHC class I/peptide complexes to host CD8 T cells. Note that the high alloreactive precursor frequency is attributed largely to the direct CD4 and CD8 T-cell pathways. (3) Indirect (host MHC-restricted) CD8 T-cell activation. In this case, antigens (generically termed “X”) derived from donor cells are processed and re-presented in association with MHC class I molecules on host-type APC. This pathway, also referred to as “cross-priming,” represents cases in which exogenous antigens enter the MHC class I processing pathway. Although largely disregarded in the past, this pathway may prove to be of greater biological significance than previously considered. (4) Indirect CD4 T-cell activation. This is probably the predominant pathway of responses to most foreign antigens. In this case, graft-derived antigens (“X”) are acquired by host-type APCs and re-presented in association with MHC class II molecules. It is generally accepted that exogenous antigens primarily gain access to the MHC class II processing pathway and so primarily induce CD4 T-cell activation.

10.1128/9781555818043/fig5-1_thmb.gif
10.1128/9781555818043/fig5-1.gif
Image of Figure 1
Figure 1

Direct and indirect pathways of graft antigen presentation. Optimal T-lymphocyte activation requires T-cell receptor recognition of processed peptide antigens complexed with MHC molecules plus appropriate secondary costimulatory signals provided by the antigen-presenting cell (APC). Four potential scenarios are depicted whereby CD4 or CD8 T cells can be activated in response to graft-derived antigens: (1) Direct (donor MHC-restricted) CD4 T-cell activation. In this case, the donor-type APC directly presents its own repertoire of peptides associated with MHC class II molecules to specific CD4 T cells. (2) Direct CD8 T-cell activation. Donor APCs directly present MHC class I/peptide complexes to host CD8 T cells. Note that the high alloreactive precursor frequency is attributed largely to the direct CD4 and CD8 T-cell pathways. (3) Indirect (host MHC-restricted) CD8 T-cell activation. In this case, antigens (generically termed “X”) derived from donor cells are processed and re-presented in association with MHC class I molecules on host-type APC. This pathway, also referred to as “cross-priming,” represents cases in which exogenous antigens enter the MHC class I processing pathway. Although largely disregarded in the past, this pathway may prove to be of greater biological significance than previously considered. (4) Indirect CD4 T-cell activation. This is probably the predominant pathway of responses to most foreign antigens. In this case, graft-derived antigens (“X”) are acquired by host-type APCs and re-presented in association with MHC class II molecules. It is generally accepted that exogenous antigens primarily gain access to the MHC class II processing pathway and so primarily induce CD4 T-cell activation.

Citation: Gill R. 2001. Cellular Immune Responses to Xenografts, p 99-115. In Platt J (ed), Xenotransplantation. ASM Press, Washington, DC. doi: 10.1128/9781555818043.ch5
Permissions and Reprints Request Permissions
Download as Powerpoint
/content/10.1128/9781555818043.chap5.fig5-2
Figure 2

Potential T-cell-dependent pathways of graft destruction. CD4 T cells are considered to be major participants in triggering antigen-specific responses to xenografts (see text). CD4 T cells can respond either directly to donor-type APCs or indirectly to graft-derived antigens presented by host APCs. Both of these responses themselves may participate in tissue injury. Direct CD4 T cells would be capable of TCR engagement of MHC class II antigens expressed by donor APCs and vascular endothelium. Indirect CD4 T cells would interact with graft antigens presented by autologous APCs, possibly producing local inflammatory tissue damage. Alternatively, CD4 T cells may collaborate with other lymphocyte subpopulations that can participate in graft rejection. On one hand, the “direct” type CD4 T cell has been chiefly implicated as helping to activate CD8 lymphocytes, leading to a graft-specific cytotoxic T-cell (CTL) response. Alternatively, “indirect” CD4 T cells are the key helper cells for B cells presenting graft-derived antigens, resulting in a graft-specific antibody response.

10.1128/9781555818043/fig5-2_thmb.gif
10.1128/9781555818043/fig5-2.gif
Image of Figure 2
Figure 2

Potential T-cell-dependent pathways of graft destruction. CD4 T cells are considered to be major participants in triggering antigen-specific responses to xenografts (see text). CD4 T cells can respond either directly to donor-type APCs or indirectly to graft-derived antigens presented by host APCs. Both of these responses themselves may participate in tissue injury. Direct CD4 T cells would be capable of TCR engagement of MHC class II antigens expressed by donor APCs and vascular endothelium. Indirect CD4 T cells would interact with graft antigens presented by autologous APCs, possibly producing local inflammatory tissue damage. Alternatively, CD4 T cells may collaborate with other lymphocyte subpopulations that can participate in graft rejection. On one hand, the “direct” type CD4 T cell has been chiefly implicated as helping to activate CD8 lymphocytes, leading to a graft-specific cytotoxic T-cell (CTL) response. Alternatively, “indirect” CD4 T cells are the key helper cells for B cells presenting graft-derived antigens, resulting in a graft-specific antibody response.

Citation: Gill R. 2001. Cellular Immune Responses to Xenografts, p 99-115. In Platt J (ed), Xenotransplantation. ASM Press, Washington, DC. doi: 10.1128/9781555818043.ch5
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555818043.chap5
1. Alter, B. J.,, and F. H. Bach. 1990. Cellular basis of the proliferative response of human T cells to mouse xenoantigens. J. Exp. Med. 171: 333– 338.
2. Arakawa, K.,, T. Akami,, M. Okamoto,, K. Akioka,, P. C. Lee,, Y. Sugano,, J. Kamei,, T. Suzuki,, H. Nagase,, Y. Tsuchihashi,, and T. Oka. 1994. Prolongation of heart xenograft survival in the NK-deficient rat. Transplant. Proc. 26: 1266– 1267.
3. Auchincloss, H., Jr.,, R. Moses,, D. Conti,, T. Sundt,, C. Smith,, D. H. Sachs,, and H. J. Winn. 1990. Rejection of transgenic skin expressing a xeno-class I antigen is CD4-dependent and CD8-independent. Transplant. Proc. 22: 1059– 1060.
4. Auchincloss, H. J. 1998. Xenogeneic transplantation: a review. Transplantation 46: 1– 20.
5. Auchincloss, H. J. 1990. Xenografting: a review. Transplant. Rev. 4: 14– 27.
6. Bancroft, A. J.,, A. N. McKenzie,, and R. K. Grencis. 1998. A critical role for IL-13 in resistance to intestinal nematode infection. J. Immunol. 160: 3453– 3461.
7. Barzaga-Gilbert, E.,, D. Grass,, S. Lawrence,, P. Peterson,, E. Lacy,, and V. Engelhard. 1992. Species specificity and augmentation of responses to class II major histocompatibility complex molecules in human CD4 transgenic mice. J. Exp. Med. 175: 1707– 1715.
8. Benda, B.,, A. Karlsson-Parra,, A. Ridderstad,, and O. Korsgren. 1996. Xenograft rejection of porcine islet-like cell clusters in immunoglobulin- or Fc-receptor y-deficient mice. Transplantation 62: 1207– 1211.
9. Bennett, S. R. M.,, F. R. Carbone,, F. Kararaalis,, R. A. Flavell,, J. F. A. P. Miller,, and W. R. Heath. 1998. Help for cytotoxic-T-cell responses is mediated by CD40 signalling. Nature 393: 478– 480.
10. Bennett, S. R. M.,, F. R. Carbone,, F. Karamalis,, J. F. A. P. Miller,, and W. R. Heath. 1997. Induction of a CD8 + cytotoxic T lymphocyte response by cross-priming requires cognate CD4 + T cell help. J. Exp. Med. 186: 65– 70.
11. Blakely, M. L.,, W. J. Van der Werf,, M. C. Berndt,, A. P. Dalmasso,, F. H. Bach,, and W. W. Hancock. 1994. Activation of intragraft endothelial and mononuclear cells during discordant xenograft rejection. Transplantation 58: 1059– 1066.
12. Bravery, C. A.,, P. Batten,, M. H. Yacoub,, and M. L. Rose. 1995. Direct recognition of SLA- and HLA-like class II antigens on porcine endothelium by human T cells results in T cell activation and release of interleukin-2. Transplantation 60: 1024– 1033.
13. Bretscher, P.,, and M. Cohn. 1970. A theory of self-nonself discrimination. Science 169: 1042– 1049.
14. Brossart, P.,, and M. J. Bevan. 1997. Presentation of exogenous protein antigens on major histocompatibility complex class I molecules by dendritic cells: pathway of presentation and regulation by cytokines. Blood 90: 1594– 1599.
15. Byrne, G. W.,, K. R. McCurry,, M. J. Martin,, S. M. McClellan,, J. L. Platt,, and J. S. Logan. 1997. Transgenic pigs expressing human CD59 and decay accelerating factor produce an intrinsic barrier to complement-mediated damage. Transplantation 63: 149– 155.
16. Calne, R. Y. 1970. Organ transplantation between widely disparate species. Transplant. Proc. 2: 550.
17. Candinas, D.,, S. Belliveau,, N. Koyamada,, T. Miyatake,, P. Hechenleitner,, W. Mark,, F. H. Bach,, and W. W. Hancock. 1996. T cell independence of macrophage and natural killer cell infiltration, cytokine production, and endothelial activation during delayed xenograft rejection. Transplantation 62: 1920– 1927.
18. Chen, C.,, A. Gault,, L. Shen,, and N. Nabavi. 1994. Molecular cloning and expression of early T cell costimulatory molecule-1 and its characterization as B7-2 molecule. J. Immunol. 152: 4929– 936.
19. Chen, Z.,, S. Cobbold,, S. Metcalfe,, and H. Waldmann. 1992. Tolerance in the mouse to major histocompatibility complex-mismatched heart allografts, and to rat heart xenografts, using monoclonal antibodies to CD4 and CD8. Eur. J. Immunol. 22: 805– 810.
20. Chitilian, H. V.,, T. M. Laufer,, K. Stenger,, S. Shea,, and H. J. Auchincloss. 1998. The strength of cell-mediated xenograft rejection in the mouse is due to the CD4+ indirect response. Xenotransplantation 5: 93– 98.
21. Chu, G.,, J. F. Markmann,, M. Ahn,, E. Chang,, R. P. DeMatteo,, R. J. Ketchum,, K. I. Brayman,, S. Deng,, and C. F. Barker. 1997. Xenogeneic but not allogeneic pancreatic islet graft survival in recipients lacking humoral immunity and major histocompatibility complex class II antigens. Transplant. Proc. 29: 901– 902.
22. Clayton, L. K.,, M. Sieh,, D. A. Pious,, and E. L. Reinherz. 1989. Identification of residues affecting class II versus HIV-1 gpl20 binding. Nature 339: 548.
23. Collins, M. K. L. 1989. Species specificity of interleukin 2 binding to individual receptor components. Eur. J. Immunol. 19: 1517– 1520.
24. Coulombe, M.,, H. Yang,, S. Guerder,, R. A. Flavell,, K. J. Lafferty,, and R. G. Gill. 1996. Tissue immunogenicity. The role of MHC antigen and the lymphocyte costimulator B7-1. J. Immunol. 157: 4790– 4795.
25. Coulombe, M.,, H. Yang,, L. A. Wolf,, and R. G. Gill. 1999. Tolerance to antigen-presenting cell-depleted islet allografts is CD4 T cell dependent. J. Immunol. 162: 2503– 2510.
26. Damle, N. K.,, K. Klussman,, P. S. Linsley,, and A. Aruffo. 1992. Differential costimulatory effects of adhesion molecules B7, ICAM-1, LFA-3, and VCAM-1 on resting and antigen-primed CD4+ T lymphocytes. J. Immunol. 148: 1985– 1992.
27. Deng, S.,, R. J. Ketchum,, T. Kucher,, M. Weber,, A. Naji,, and K. L. Brayman. 1997. NK cells, macrophages, and humoral immune responses are dominant in primary nonfunction of islet grafts in the dog-to-rat xenotransplant model. Transplant. Proc. 29: 2062– 2063.
28. Desai, N. M.,, H. Bassiri,, J. Kim,, B. H. Roller,, O. Smithies,, C. F. Barker,, A. Naji,, and J. F. Markman. 1993. Islet allograft, islet xenograft, and skin allograft survival in CD8 + T lymphocyte-deficient mice. Transplantation 55: 718– 722.
29. Desai, N. M.,, H. Bassiri,, J. S. Odorico,, B. H. Roller,, O. Smithies,, A. Naji,, C. F. Barker,, and J. F. Markmann. 1993. Pancreatic islet allograft and xenograft survival in CD8+ T-lymphocyte-deficient recipients. Transplant. Proc. 25: 961– 962.
30. Donnelly, C. E.,, C. Yatko,, E. W. Johnson,, and A. S. Edge. 1997. Human natural killer cells account for non-MHC class I-restricted cytolysis of porcine cells. Cell Immunol. 175: 171– 178.
31. Dorling, A.,, R. Binns,, and R. I. Lechler. 1996. Significant primary indirect human T-cell anti-pig xenoresponses observed using immature porcine dendritic cells and SLA-class II- negative endothelial cells. Transplant Proc. 28: 654.
32. Duncan, D. D.,, and S. L. Swain. 1994. Role of antigen-presenting cells in the polarized development of helper T cell subsets: evidence for differential cytokine production by Th0 cells in response to antigen presentation by B cells and macrophages. Eur. J. Immunol. 24: 2506– 2514.
33. Elwood, E. T.,, C. P. Larsen,, H. R. Cho,, M. Corbascio,, S. C. Ritchie,, D. Z. Alexander,, C. Tucker-Burden,, P. S. Linsley,, A. Aruffo,, D. Hollenbaugh,, K. J. Winn,, and T. C. Pearson. 1998. Prolonged acceptance of concordant and discordant xenografts with combined CD40 and CD28 pathway blockade. Transplantation 65: 1422– 1428.
34. Feng, S.,, R. R. Quickel,, J. HoUister-Lock,, M. McLeod,, S. Bonner-Weir,, R. C. Mulligan,, and G. C. Weir. 1999. Prolonged xenograft survival of islets infected with small doses of adenovirus expressing CTLA4Ig. Transplantation 67: 1607– 1613.
35. Finkelman, F. D.,, T. Shea-Donohue,, J. Goldhill,, C. A. Sullivan,, S. C. Morris,, K. B. Madden,, W. C. Cause,, and J. F. Urban, Jr. 1997. Cytokine regulation of host defense against parasitic gastrointestinal nematodes: lessons from studies with rodent models. Annu. Rev. Immunol. 15: 505– 533.
36. Friedman, T.,, A. Shimizu,, R. N. Smith,, R. B. Colvin,, J. D. Seebach,, D. H. Sachs,, and J. Iacomini. 1999. Human CD4+ T cells mediate rejection of porcine xenografts. J. Immunol. 162: 5256– 5262.
37. Friedman, T.,, R. N. Smith,, R. B. Colvin,, and J. Iacomini. 1999. A critical role for human CD4+ T-cells in rejection of porcine islet cell xenografts. Diabetes 48: 2340– 2348.
38. Gill, R.,, L. Wolf,, D. Daniel,, and M. Coulombe. 1994. CD4 T cells are both necessary and sufficient for islet xenograft rejection. Transplant. Proc. 26: 1203.
39. Gill, R. G. 1992. The role of direct and indirect antigen presentation in the response to islet xenografts. Transplant. Proc. 24: 642– 643.
40. Gill, R. G.,, and M. Coulombe. 1992. Rejection of pancreatic islet xenografts does not require CD8+ T-lymphocytes. Transplant. Proc. 24: 2877– 2878.
41. Gill, R. G.,, and L. Wolf. 1995. Immunobiology of cellular transplantation. Cell Transplant. 4: 361– 370.
42. Goodman, D. J.,, M. von Albertini,, A. Willson,, M. T. Millan,, and F. H. Bach. 1996. Direct activation of porcine endothelial cells by human natural killer cells. Transplantation 61: 763– 771.
43. Gordon, E. J.,, T. G. Markees,, N. E. Phillips,, R. J. Noelle,, L. D. Shultz,, J. P. Mordes,, A. A. Rossini,, and D. L. Greiner. 1998. Prolonged survival of rat islet and skin xenografts in mice treated with donor splenocytes and anti-CD154 monoclonal antibody. Diabetes 47: 1199– 1206.
44. Greenstein, J. L.,, J. A. Foran,, J. C. Gorga,, and S. J. Burakoff. 1986. The role of T cell accessory molecules in the generation of class II-specific xenogeneic cytolytic T cells. J. Immunol. 136: 2358– 2363.
45. Grewal, I. S.,, H. G. Foellmer,, K. D. Grewal,, J. Xu,, F. Hardardottir,, J. L. Baron,, C. A. Janeway, Jr.,, and R. A. Flavell. 1996. Requirement for CD40 ligand in costimulation induction, T cell activation, and experimental allergic encephalomyelitis. Science 273: 1864– 1867.
46. Guerder, S.,, D. E. Picarella,, P. S. Linsley,, and R. A. Flavell. 1994. Costimulator B7-1 confers antigen-presenting-cell function to parenchymal tissue and in conjunction with tumor necrosis factor a leads to autoimmunity in transgenic mice. Proc. Natl. Acad. Sci. USA 91: 5138– 5142.
47. Gustafsson, K.,, S. Germana,, F. Hirsch,, K. Pratt,, C. LeGuern,, and D. H. Sachs. 1990. Structure of miniature swine class II DRB genes: conservation of hypervariable amino acid residues between distantly related mammalian species. Proc. Natl. Acad. Sci USA 87: 9798– 9802.
48. Hamelmann, W.,, D. W. R. Gray,, T. D. J. Cairns,, T. Ozasa,, D. J. P. Ferguson,, A. Cahill,, K. I. Welsh,, and P. J. Morris. 1994. Immediate destruction of xenogeneic islets in a primate model. Transplantation 58: 1109– 1114.
49. Hao, L.,, Y. Wang,, R. G. Gill,, and K. J. Lafferty. 1987. Role of the L3T4+ T cell in allograft rejection. J. Immunol. 139: 4022– 026.
50. Herrlinger, K. R.,, V. Eckstein,, W. Muller-Ruchholtz,, and K. Ulrichs. 1996. Human T-cell activation is mediated predominantly by direct recognition of porcine SLA and involves accessory molecule interaction of ICAM1/LFA1 and CD2/LFA3. Transplant. Proc. 28: 650.
51. Inverardi, L.,, B. Clissi,, A. L. Stolzer,, J. R. Bender,, M. S. Sandrin,, and R. Pardi. 1997. Human natural killer lymphocytes directly recognize evolutionarily conserved oligosaccharide ligands expressed by xenogeneic tissues. Transplantation 63: 1318– 1330.
52. Irwin, M. J.,, W. R. Heath,, and L. A. Sherman. 1989. Species-restricted interactions between CD8 and the α3 domain of class I influence the magnitude of the xenogeneic response. J. Exp. Med. 170: 1091– 1101.
53. Itescu, S.,, P. Kwiatkowski,, S. F. Wang,, T. Blood,, O. P. Minanov,, S. Rose,, and R. E. Michler. 1996. Circulating human mononuclear cells exhibit augmented lysis of pig endothelium after activation with interleukin 2. Transplantation 62: 1927– 1933.
54. June, C. H.,, J. A. Ledbetter,, P. S. Linsley,, and C. B. Thompson. 1990. Role of the CD28 receptor in T-cell activation. Immunol. Today 11: 211– 216.
55. Kalinke, U.,, B. Arnold,, and G. J. Hammerling. 1990. Strong xenogeneic HLA response in transgenic mice after introducing an a3 domain into HLA B27. Nature 348: 642– 644.
56. Karlsson-Parra, A.,, A. Ridderstad,, A. C. Wallgren,, E. Moller,, H. G. Ljunggren,, and O. Korsgren. 1996. Xenograft rejection of porcine islet-like cell clusters in normal and natural killer cell-depleted mice. Transplantation 61: 1313– 1320.
57. Kaufman, D. S.,, C. S. Kong,, J. A. Shizuru,, A. K. Gregory,, and C. G. Fathman. 1988. Use of anti-L3T4 and anti-la treatments for prolongation of xenogeneic islet transplants. Transplantation 46: 210– 215.
58. Kawamura, T.,, T. Niguma,, J. H. J. Fechner,, R. Wolber,, M. A. Beeskau,, D. A. Hullett,, H. W. Sollinger,, and W. J. Burlingham. 1992. Chronic human skin graft rejection in severe combined immunodeficient mice engrafted with human PBL from an HLA-presensitized donor. Transplantation 53: 659– 665.
59. Kenyon, N. S.,, M. Chatzipetrou,, M. Masetti,, A. Ranuncoli,, M. Oliveira,, J. L. Wagner,, A. D. Kirk,, D. M. Harlan,, L. C. Burkly,, and C. Ricordi. 1999. Long-term survival and function of intrahepatic islet allografts in rhesus monkeys treated with humanized anti-CD154. Proc. Natl. Acad. Sci. USA 96: 8132– 8137.
60. Kievits, F.,, J. Wijffels,, W. Lokhorst,, and P. Ivany. 1988. Recognition of xeno-(HLA, SLA) major histocompatibility complex antigens by mouse cytotoxic T cells is not H-2 restricted: a study with transgenic mice. Proc. Natl. Acad. Sci. USA 86: 617– 620.
61. Kirk, A. D.,, D. M. Harlan,, N. N. Armstrong,, T. A. Davis,, Y. Dong,, G. S. Gray,, X. Hong,, D. Thomas,, J. H. Fechner, Jr.,, and S. J. Knechtle. CTLA4-Ig and anti-CD40 ligand prevent renal allograft rejection in primates. Proc. Natl. Acad. Sci. USA 94: 8789– 8794.
62. Kirk, A. D.,, J. S. Heinle,, J. R. Mault,, and F. Sanfllippo. 1993. Ex vivo characterization of human anti-porcine hyperacute cardiac rejection. Transplantation 56: 785– 793.
63. Kirk, A. D.,, R. A. Li,, M. S. Kinch,, K. A. Abernethy,, C. Doyle,, and R. R. Bollinger. 1993. The human antiporcine cellular repertoire. In vitro studies of acquired and innate cellular responsiveness. Transplantation 55: 924– 931.
64. Korbutt, G. S.,, L. Aspeslet,, Z. Ao,, G. L. Warnock,, J. Ezekowitz,, A. Koshal,, R. V. Rajotte,, and R. W. Yatscoff. 1996. Porcine islet cell antigens are recognized by xenoreactive natural human antibodies of both IgG and IgM subtypes. Transplant. Proc. 28: 837– 838.
65. Korngold, R.,, and J. Sprent. 1985. Surface markers of T cells causing lethal graft-vs-host disease to class I vs class II H-2 differences. J. Immunol. 135: 3004– 3010.
66. Krieger, N. R.,, H. Ito,, and C. G. Fathman. 1997. Rat pancreatic islet and skin xenograft survival in CD4 and CD8 knockout mice. J. Autoimmun. 10: 309– 315.
67. Kurts, C.,, F. R. Carbone,, M. Barnden,, E. Blanas,, J. Allison,, W. R. Heath,, and J. F. A. P. Miller. 1997. CD4+ T cell help impairs CD8+ T cell deletion induced by cross-presentation of self-antigens and favors autoimmunity. J. Exp. Med. 186: 2057– 2062.
68. Kurts, C.,, W. R. Heath,, F. R. Carbone,, J. Allison,, J. F. A. P. Miller,, and H. Kosaka. 1996. Constitutive class I-restricted exogenous presentation of self antigens in vivo. J. Exp. Med. 184: 923– 930.
69. Lacy, P. E.,, C. Ricordi,, and E. H. Finke. 1989. Effect of transplantation site and αL3T4 treatment on survival of rat, hamster, and rabbit islet xenografts in mice. Transplantation 47: 761– 766.
70. Lafferty, K. J.,, and M. A. S. Jones. 1969. Reactions of the graft-versus-host (GVH) type. Aust. J. Exp. Biol. Med. Sci. 47: 17– 54.
71. Lafferty, K. J.,, S. J. Prowse,, and C. J. Simeonovic. 1983. Immunobiology of tissue transplantation: a return to the passenger leukocyte concept. Annu. Rev. Immunol. 1: 143– 173.
72. Lafferty, K. J.,, H. S. Warren,, J. A. Woolnough,, and D. W. Talmage. 1978. Immunological induction of T lymphocytes: role of antigen and the costimulator. Blood Cells 4: 395– 404.
73. Lafferty, K. L.,, and A. J. Cunningham. 1975. A new analysis of allogeneic interactions. Aust. J. Exp. Biol. Med. Sci. 53: 27– 42.
74. Lanier, L. L. 1998. NK cell receptors. Annu. Rev. Immunol. 16: 359– 393.
75. Larsen, C. P.,, E. T. Elwood,, D. Z. Alexander,, S. C. Ritchie,, R. Hendrix,, C. Tucker-Burden,, H. R. Cho,, A. Aruffo,, D. Hollenbaugh,, P. S. Linsley,, K. J. Winn,, and T. C. Pearson. 1996. Long-term acceptance of skin and cardiac allografts after blocking CD40 and CD28 pathways. Nature 381: 434– 438.
76. Law, Y. M.,, R. S. M. Yeung,, C. Mamalaki,, D. Kioussis,, T. W. Mak,, and R. A. Flavell. 1994. Human CD4 restores normal T cell development and function in mice deficient in murine CD4. J. Exp. Med. 179: 1233– 1242.
77. Lenschow, D. J.,, Y. Zeng,, J. R. Thistlethwaite,, A. Montag,, W. Brady,, M. G. Gibson,, P. S. Linsley,, and J. A. Bluestone. 1992. Long-term survival of xenogeneic pancreatic islet grafts induced by CTLA4Ig. Science 257: 789– 792.
78. Leventhal, J. R.,, A. J. Matas,, L. H. Sun,, S. Reif,, R. M. D. Bolman,, A. P. Dalmasso,, and J. L. Platt. 1993. The immunopathology of cardiac xenograft rejection in the guinea pig-to-rat model. Transplantation 56: 1– 8.
79. Lin, Y.,, M. P. Soares,, K. Sato,, K. Takigami,, E. Csizmadia,, J. Anrather,, and F. H. Bach. 1999. Rejection of cardiac xenografts by CD4+ or CD8+ T cells. J. Immunol. 162: 1206– 1212.
80. Lin, Y.,, M. Vandeputte,, and M. Waer. 1997. Natural killer cell- and macrophage-mediated rejection of concordant xenografts in the absence of T and B cell responses. J. Immunol. 158: 5658– 5667.
81. Louis, J.,, H. Himmelrich,, C. Parra-Lopez,, F. Tacchini-Cottier,, and P. Launois. 1998. Regulation of protective immunity against Leishmania major in mice. Curr. Opin. Immunol. 10: 459– 464.
82. Lucas, P. J.,, G. M. Shearer,, S. Neudorf,, and R. E. Gress. 1990. The human anti-murine xenogeneic cytotoxic response. I. Dependence on responder antigen-presenting cells. J. Immunol. 144: 4548– 4554.
83. Mandel, T. E.,, and M. Koulmanda. 1992. The survival of xeno-, alio- and isografts in NOD mice and xenografts in other strains, after immunosuppression with anti-CD4 monoclonal antibody. Diab. Nutr. Metab. 5( Suppl. l): 91– 96.
84. Markmann, J. E.,, H. Bassiri,, N. M. Desai,, J. S. Odorico,, J. I. Kim,, B. H. Koller,, O. Smithies,, and C. F. Barker. 1992. Indefinite survival of MHC class I-deficient murine pancreatic islet allografts. Transplantation 54: 1085– 1089.
85. Markmann, J. F.,, L. Campos,, A. Bhandoola,, J. I. Kim,, N. M. Desai,, H. Bassiri,, B. R. Claytor,, and C. F. Barker. 1994. Genetically engineered grafts to study xenoimmunity: a role for indirect antigen presentation in the destruction of major histocompatibility complex antigen deficient xenografts. Surgery 116: 242– 248.
86. McCune, J. M.,, R. Namikawa,, H. Kaneshima,, L. D. Shultz,, M. Lieberman,, and I. L. Weissman. 1988. The SCID-hu mouse: murine model for the analysis of human hematolymphoid differentiation and function. Science 241: 1632– 1639.
87. Medbury, H. J.,, M. Hibbins,, A. M. Lehnert,, W. J. Hawthorne,, J. R. Chapman,, T. E. Mandel,, and P. J. O'Connell. 1997. The cytokine and histological response in islet xenograft rejection is dependent upon species combination. Transplantation 64: 1307– 1314.
88. Mombaerts, P.,, J. Iacomini,, R. S. Johnson,, K. Herrup,, S. Tonegawa,, and V. E. Papaioannou. 1992. RAG-1-deficient mice have no mature B and T lymphocytes. Cell 68: 869– 877.
89. Morris, C. F.,, C. J. Simeonovic,, M.-C. Fung,, J. D. Wilson,, and A. J. Hapel. 1995. Intragraft expression of cytokine transcripts during pig proislet xenograft rejection and tolerance in mice. J. Immunol. 154: 2470– 2482.
90. Moses, R. D.,, R. N. Pierson III,, H. J. Winn,, and J. H. Auchincloss. 1990. Xenogeneic proliferation and lymphokine production are dependent on CD4+ helper T cells and self antigen-presenting cells in the mouse. J. Exp. Med. 172: 567– 575.
91. Moses, R. D.,, H. J. Winn,, and H. J. Auchincloss. 1992. Evidence that multiple defects in cell-surface molecule interactions across species differences are responsible for diminished xenogeneic T cell responses. Transplantation 53: 203– 209.
92. Mueller, J. P.,, M. A. Giannoni,, S. L. Hartman,, E. A. Elliott,, S. P. Squinto,, L. A. Matis,, and M. J. Evans. 1997. Humanized porcine VCAM-specific monoclonal antibodies with chimeric IgG2/G4 constant regions block human leukocyte binding to porcine endothelial cells. Mol. Immunol. 34: 441– 452.
93. Murphy, B.,, H. Auchincloss, Jr.,, C. B. Carpenter,, and M. H. Sayegh. 1996. T cell recognition of xeno-MHC peptides during concordant xenograft rejection. Transplantation 61: 1133– 1137.
94. Pascher, A.,, C. Poehlein,, M. Storck,, R. Prestel,, J. Mueller-Hoecker,, D. J. White,, D. Abendroth,, and C. Hammer. 1997. Immunopathological observations after xenogeneic liver perfusions using donor pigs transgenic for human decay-accelerating factor. Transplantation 64: 384– 391.
95. Pearson, T. C.,, D. Z. Alexander,, K. J. Winn,, P. S. Linsley,, R. P. Lowry,, and C. P. Larsen. 1994. Transplantation tolerance induced by CTLA4-Ig. Transplantation 57: 1701– 1706.
96. Pearson, T. C.,, J. C. Madsen,, C. P. Larsen,, P. J. Morris,, and K. J. Wood. 1992. Induction of transplantation tolerance in adults using donor antigen and anti-CD4 monoclonal antibody. Transplantation 54: 475– 483.
97. Piccotti, J. R.,, S. Y. Chan,, A. M. VanBuskirk,, E. J. Eichwald,, and D. K. Bishop. 1997. Are Th2 helper T lymphocytes beneficial, deleterious, or irrelevant in promoting allograft survival? Transplantation 63: 619– 624.
98. Pierson, R. N., III,, H. J. Winn,, P. S. Russell,, and H. Auchincloss. 1989. Xenogeneic skin graft rejection is especially dependent on CD4+ T cells. J. Exp. Med. 170: 991– 996.
99. Platt, J. L.,, and F. H. Bach. 1991. The barrier to xenotransplantation. Transplantation 52: 937– 947.
100. Platt, J. L.,, S. S. Lin,, and C. G. McGregor. 1998. Acute vascular rejection. Xenotransplantation 5: 169– 175.
101. Raisanen-Sokolowski, A.,, P. L. Mottram,, T. Glysing-Jensen,, A. Satoskar,, and M. E. Russell. 1997. Heart transplants in interferon-y, interleukin 4, and interleukin 10 knockout mice: recipient environment alters graft rejection. J. Clin. Invest. 100: 2449– 2456.
102. Ridge, J. P.,, F. Di Rosa,, and P. Matzinger. 1998. A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell. Nature 393: 474– 478.
103. Rocha, B.,, and H. von Boehmer. 1991. Peripheral selection of the T cell repertoire. Science 251: 1225– 1228.
104. Rollins, S. A.,, S. P. Kennedy,, A. J. Chodera,, E. A. Elliott,, G. B. Zavoico,, and L. A. Matis. 1994. Evidence that activation of human T cells by porcine endothelium involves direct recognition of porcine SLA and costimulation by porcine ligands for LFA-1 and CD2. Transplantation 57: 1709– 1716.
105. Rouleau, M.,, R. Namikawa,, S. Antonenko,, N. Carballido-Perrig,, and M. G. Roncarolo. 1996. Antigen-specific cytotoxic T cells mediate human fetal pancreas allograft rejection in SCID-hu mice. J. Immunol. 157: 5710– 5720.
106. Sachs, D. H.,, and F. H. Bach. 1990. Immunology of xenograft rejection. Human Immunol. 28: 245– 251.
107. Saleem, S.,, B. T. Konieczny,, R. P. Lowry,, F. K. Baddoura,, and F. G. Lakkis. 1996. Acute rejection of vascularized heart allografts in the absence of IFN γ. Transplantation 62: 1908– 1911.
108. Sandberg, J.-O.,, B. Benda,, N. Lycke,, and O. Korsgren. 1997. Xenograft rejection of porcine islet-like cell clusters in normal, interferon- γ, and interferon- γ receptor deficient mice. Transplantation 63: 1446– 1452.
109. Scharton, T. M.,, and P. Scott. 1993. Natural killer cells are a source of interferon gamma that drives differentiation of CD4+ T cell subsets and induces early resistance to Leishmania major in mice. J. Exp. Med. 178: 567– 577.
110. Schoenberger, S. P.,, R. E. M. Toes,, E. I. H. van der Voort,, R. Offringa,, and C. J. M. Melief. 1998. T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions. Nature 393: 480– 483.
111. Schwartz, R. H. 1992. Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy. Cell 71: 1065– 1068.
112. Scully, R.,, S. Qin,, S. Cobbold,, and H. Waldmann. 1994. Mechanisms in CD4 antibody-mediated transplantation tolerance: kinetics of induction, antigen dependency and role of regulatory T cells. Eur. J. Immunol. 24: 2383– 2392.
113. Seebach, J. D.,, C. Comrack,, S. Germana,, C. LeGuern,, D. H. Sachs,, and H. DerSimonian. 1997. HLA-Cw3 expression on porcine endothelial cells protects against xenogeneic cytotoxicity mediated by a subset of human NK cells. J. Immunol. 159: 3655– 3661.
114. Shishido, S.,, B. Naziruddin,, T. Howard,, and T. Mohanakumar. 1997. Recognition of porcine major histocompatibility complex class I antigens by human CD8+ cytolytic T cell clones. Transplantation 64: 340– 346.
115. Shishido, S.,, B. Naziruddin,, X. C. Xu,, T. Howard,, and T. Mohanakumar. 1998. Indirect recognition of porcine xenoantigens by human CD4+ T cell clones. Transplantation 65: 706– 712.
116. Shizuru, J. A.,, A. K. Gregory,, C. T. B. Chao,, and C. G. Fathman. 1987. Islet allograft survival after a single course of treatment of recipient with antibody to L3T4. Science 237: 278– 280.
117. Shizuru, J. A.,, K. B. Seydal,, T. F. Flavin,, A. P. Wu,, C. C. Kong,, E. G. Hoyt,, N. Fujimoto,, M. E. Billingham,, V. A. Starnes,, and C. G. Fathman. 1990. Induction of donor specific unresponsiveness to cardiac allografts in rats by pretransplant anti-CD4 monoclonal antibody therapy. Transplantation 50: 366– 371.
118. Simeonovic, C. J.,, M. J. Townsend,, J .D. Wilson,, K. U. McKenzie,, A. J. Ramsay,, K. I. Matthaei,, D.A. Mann,, and I. G. Young. 1997. Eosinophils are not required for the rejection of neovascularized fetal pig proislet xenografts in mice. J. Immunol. 158: 2490– 2499.
119. Simeonovic, C. J.,, and J. D. Wilson. 1992. CD4+ T-cell depletion in mice facilitates induction of tolerance to pig proislet xenografts: a comparison of NOD and CBA/H recipient models. Diab. Nutr. Metab. 5( Suppl. 1): 133– 138.
120. Simon, A. R.,, A. N. Warrens,, N. P. Yazzie,, J. D. Seebach,, D. H. Sachs,, and M. Sykes. 1998. Cross-species interaction of porcine and human integrins with their respective ligands: implications for xenogeneic tolerance induction. Transplantation 66: 385– 394.
121. Smyth, M. J.,, and J. M. Kelly. 1999. Accessory function for NK1.1 + natural killer cells producing interferon-y in xenospecific cytotoxic T lymphocyte differentiation. Transplantation 68: 840– 843.
122. Sobel, D. O.,, C. H. Ewel,, B. Zeligs,, V. Abbassi,, J. Rossio,, and J. A. Bellanti. 1994. Poly I:C induction of a-interferon in the diabetes-prone BB and normal Wistar rats. Dose-response relationships. Diabetes 43: 518– 522.
123. Swain, S. L. 1983. T cell subsets and the recognition of MHC class. Immunol. Rev. 74: 129– 142.
124. Talmage, D.,, J. Woolnough,, H. Hemmingsen,, L. Lopez,, and K. Lafferty. 1977. Activation of cytotoxic T cells by nonstimulating tumor cells and spleen cell factor(s). Proc. Natl. Acad. Sci. USA 74: 1610– 1614.
125. Torgersen, K. M.,, M. Salcedo,, J. T. Vaage,, C. Naper,, B. Rolstad,, H.-G. Ljunggren,, and P. Hoglund. 1997. Major histocompatibility complex class I-independent killing of xenogeneic targets by rat allospecific natural killer cells. Transplantation 63: 119– 123.
126. Tutt, M. M.,, W. Schuler,, W. A. Kuziel,, P. W. Tucker,, M. Bennett,, M. J. Bosma,, and V. Kumar. 1987. T cell receptor genes do not rearrange or express functional transcripts in natural killer cells of scid mice. J. Immunol. 138: 2338– 2344.
127. Vignali, D. A. A.,, J. Moreno,, D. Schiller,, and G. J. Hammerling. 1992. Species-specific binding of CD4 to the /82 domain of major histocompatibility complex class II molecules. J. Exp. Med. 175: 925– 932.
128. von Hoegen, P.,, M. C. Miceli,, B. Tourvieille,, M. Schilham,, and J. R. Parnes. 1989. Equivalence of human and mouse CD4 in enhancing antigen responses by a mouse class II-restricted T cell hybridoma. J. Exp. Med. 170: 1879– 1886.
129. Wang, Y.,, O. Pontesili,, R. G. Gill,, F. G. LaRosa,, and K. J. Lafferty. The role of CD4 + and CD8 + T cells in the destruction of islet grafts by spontaneously diabetic mice. Proc. Natl. Acad. Sci. USA 1991. 88: 527– 531.
130. Watts, T. H.,, and M. A. DeBenedette. T cell co-stimulatory molecules other than CD28. Curr. Opin. Immunol, 1999. 11: 286– 293.
131. Weber, C. J.,, M. K. Hagler,, J. T. Chryssochoos,, J. A. Kapp,, G. S. Korbutt,, R. V. Rajotte,, and P. S. Linsley. 1997. CTLA4-Ig prolongs survival of microencapsulated neonatal porcine islet xenografts in diabetic NOD mice. Cell Transplant. 6: 505– 508.
132. Wecker, H.,, H. Winn,, and H. J. Auchincloss. 1994. CD4+ T cells, without CD8+ or B lymphocytes, can reject xenogeneic skin grafts. Xenotransplantation 1: 8– 16.
133. Wilson, J. D.,, C. J. Simeonovic,, J. J. L. Ting,, and R. Ceredig. 1989. Role of CD4+ T-lymphocytes in rejection by mice of fetal pig proislet xenografts. Diabetes 38( Supp. 1): 217– 219.
134. Wolf, L.,, and R. G. Gill. 1993. Xenoreactive T-cell lines initiate pancreatic islet graft destruction in vivo. Transplant. Proc. 25: 440– 441.
135. Wolf, L. A.,, M. Coulombe,, and R. G. Gill. 1995. Donor antigen-presenting cell-independent rejection of islet xenografts. Transplantation 60: 1164– 1170.
136. Woolnough, J.,, I. Misko,, and K. J. Lafferty. 1979. Cytotoxic and proliferative lymphocyte responses to allogeneic and xenogeneic antigens in vitro. Aust. J. Exp. Bio. Med. Sci. 57: 467– 477.
137. Wren, S. M.,, S. C. Wang,, N. L. Thai,, B. Conrad,, R. A. Hoffman,, J. J. Fung,, R. L. Simmons,, and S. T. Ildstad. 1993. Evidence for early Th2 T cell predominance in xenoreactivity. Transplantation 56: 905– 911.
138. Xu, X. C.,, B. Naziruddin,, H. Sasaki,, D. M. Smith,, and T. Mohanakumar. 1999. Allele-specific and peptide-dependent recognition of swine leukocyte antigen class I by human cytotoxic T-cell clones. Transplantation 68: 473– 479.
139. Yamada, K.,, D. H. Sachs,, and H. DerSimonian. 1995. Direct and indirect recognition of pig class II antigens by human T cells. Transplant. Proc. 27: 258– 259.
140. Yamada, K.,, D. H. Sachs,, and H. DerSimonian. 1995. Human anti-porcine xenogeneic T cell response. Evidence for allelic specificity of mixed leukocyte reaction and for both direct and indirect pathways of recognition. J. Immunol. 155: 5249– 5256.
141. Yoshizawa, K.,, and A. Yano. 1984. Mouse T lymphocytes proliferative responses specific for human MHC products in mouse anti-human xenogeneic MLR. J. Immunol. 132: 2820– 2829.
142. Zelenika, D.,, E. Adams,, A. Mellor,, E. Simpson,, P. Chandler,, B. Stockinger,, H. Waldmann,, and S. P. Cobbold. 1998. Rejection of H-Y disparate skin grafts by monospecific CD4+ Thl and Th2 cells: no requirement for CD8+ T cells or B cells. J. Immunol. 161: 1868– 1874.
143. Zinkernagel, R. M.,, and P. C. Doherty. 1974. Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature 248: 701– 702.

Tables

Cellular Immune Responses to Xenografts
[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555818043.chap5-1,webId=/content/author/10.1128/9781555818043.chap5-1,properties={foaf_givenname=Ronald G., foaf_name=Ronald G. Gill, foaf_surname=Gill, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555818043.chap5-aff1]]}]]
Citation: Gill R. 2001. Cellular Immune Responses to Xenografts, p 99-115. In Platt J (ed), Xenotransplantation. ASM Press, Washington, DC. doi: 10.1128/9781555818043.ch5
/content/10.1128/9781555818043.chap5.tab5-1
Table 1

Systemic induction of NK cells does not trigger rejection of rat islet xenografts established in scid mice

10.1128/9781555818043/tab5-1_thmb.gif
10.1128/9781555818043/tab5-1.gif
Generic image for table
Table 1

Systemic induction of NK cells does not trigger rejection of rat islet xenografts established in scid mice

Citation: Gill R. 2001. Cellular Immune Responses to Xenografts, p 99-115. In Platt J (ed), Xenotransplantation. ASM Press, Washington, DC. doi: 10.1128/9781555818043.ch5

Back to top
This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error