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Chapter 29 : CD8 T Cells in Tuberculosis

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Abstract:

This chapter focuses on CD8 T cells, with an emphasis on the major histocompatibility complex (MHC) Ia-restricted T cells in tuberculosis, and also touches upon the unconventional CD8 T cells restricted by βm-associated nonclassical MHC Ib or MHC I-like molecules. Although the T cells which recognize mycobacterial glycolipids in the context of group I CD1 molecules are not only CD8 but also double negative and sometimes even CD4, they are considered in this chapter where appropriate. Importantly, dendritic cells (DC) can capture an antigen at the site of infection and transport it to draining lymph nodes, where T-cell stimulation takes place. The possible functions of CD8 T cells in the control of tuberculosis include cytokine production, macrophage activation, killing of infected cells, and killing of . The memory response to in the lungs is weak compared to that of some viral infections. A model that has been used to study memory responses is infection of mice followed by antimycobacterial drug treatment beginning 4 weeks after infection. In summary, CD8 T cells that recognize mycobacterial antigens on macrophages or DC are induced following . Given the potential for effective immune responses mediated by CD8 T cells, more researchers are using strategies that include the induction of CD8 T cells in vaccine candidates for tuberculosis. The results of these studies may provide important data on the ability of CD8 T cells to contribute to protection against this disease.

Citation: Kaufmann S, Flynn J. 2005. CD8 T Cells in Tuberculosis, p 465-474. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch29

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Bacterial Proteins
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Tumor Necrosis Factor alpha
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Major Histocompatibility Complex
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Figures

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Figure 1

Dichotomous view of the T-lymphocyte system, showing the major T-cell populations. Frequently, the MHC IIrestricted CD4 T cells and the MHC I-restricted CD8 T cells are termed “conventional T cells” whereas the γ/δ T cells and the MHC Ib and CD1-restricted T cells are often subsumed under the term “unconventional T cells.”

Citation: Kaufmann S, Flynn J. 2005. CD8 T Cells in Tuberculosis, p 465-474. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch29
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Image of Figure 2
Figure 2

The βm-dependent T cells in tuberculosis and the respective antigen-processing pathways. The βm-dependent T cells comprise classical MHC Ia-restricted CD8 T cells, nonclassical MHC Ib-restricted CD8 T cells, and the group I CD1-restricted CD8 T cells. The last of these T-cell populations sometimes is double negative (DN) or even CD4.

Citation: Kaufmann S, Flynn J. 2005. CD8 T Cells in Tuberculosis, p 465-474. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch29
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Image of Figure 3
Figure 3

Cross-priming as a mechanism of efficient stimulation of βm-dependent T cells. Macrophages infected with undergo apoptosis, leading to the formation of apoptotic blebs. These apoptotic blebs carry antigenic cargo derived from from infected cells to bystander DC, which are better equipped for antigen-specific T-cell stimulation.

Citation: Kaufmann S, Flynn J. 2005. CD8 T Cells in Tuberculosis, p 465-474. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch29
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Image of Figure 4
Figure 4

CD8 T-cell functions. CD8 T cells can activate macrophages via the release of cytokines, including IFN-γ and TNF-α, which induce phagolysosome fusion and reactive nitrogen intermediate (such as nitric oxide) production to kill intracellular . CD8 T cells can also act as CTL and lyse infected macrophages. This lysis can occur in the context of a granuloma, where released mycobacteria can be taken up and killed by activated macrophages. Perforin can mediate lysis but also enables granule-associated proteins, such as granulysin and granzymes, to enter the infected macrophage. Granulysin can directly kill intracellular . Finally, CD8 T cells can cause apoptosis of infected macrophages through a Fas/Fasligand- or TNF-α-mediated pathway.

Citation: Kaufmann S, Flynn J. 2005. CD8 T Cells in Tuberculosis, p 465-474. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch29
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