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Chapter 27 : T Cell and Dendritic Cell Immune Responses to

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Abstract:

This chapter reviews current knowledge regarding the role of dendritic cells (DCs) and T cells in the generation of protective immunity against infections. DCs function as sentinels in the innate immune system. They are the most effective antigenpresenting cells (APCs) for inducing cell-mediated immune responses and are uniquely capable of activating naive T cells. DCs phagocytose pathogens, endocytose foreign antigens, process and present antigens to T cells, and are key mediators in the initiation of adaptive immune responses. DCs are uniquely capable of decoding fungal-associated information and translating it into different adaptive Th-type immune responses. The protective immune responses correlated with accumulation of myeloid DCs in the draining lymph nodes, while nonprotective responses were associated with accumulation of lymphoid DCs. Peripheral blood mononuclear cells from HIV-infected donors have profoundly impaired proliferative and cytokine responses to cryptococcal antigens. Immunization of mice with heat-killed conferred protection against challenge in wild-type mice but did not induce protection in nude mice (lacking T cells), demonstrating the importance of T cells in protection in the central nervous system (CNS). The lungs and brain are the most common sites of infection for and . In pulmonary, systemic, and CNS infections, Th1-type cytokines are required for a protective cell-mediated immune response. The necessity of T cells for host defenses against cryptococcosis has prompted research into identifying immunoreactive cryptococcal antigens that could serve as vaccine candidates and as diagnostic reagents to measure T-cell responses in infected or at-risk patients.

Citation: Wozniak K, Levitz S. 2011. T Cell and Dendritic Cell Immune Responses to , p 387-396. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch27

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Major Histocompatibility Complex
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Image of FIGURE 1
FIGURE 1

Overview of the link between innate recognition by DCs and the development of adaptive CD4 T-cell immunity to . The immune response begins with DC phagocytosis of , followed by entry into the endolysosomal pathway. Antigen is then processed and presented to naive T cells in the presence of costimulatory molecules and polarizing cytokines. This leads to T-cell activation, Th skewing, and lymphoproliferation. Not shown in the figure are Treg cells, whose role in cryptococcal infections is poorly defined.

Citation: Wozniak K, Levitz S. 2011. T Cell and Dendritic Cell Immune Responses to , p 387-396. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch27
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Image of FIGURE 2
FIGURE 2

Electron microscopy of phagocytosis by murine bonemarrowderived DCs. (A, B) Scanning electron microscopy of in the process of being phagocytosed by DCs. (C) Transmission electron microscopy of a DC that has completely phagocytosed one and has partially internalized a second yeast cell.

Citation: Wozniak K, Levitz S. 2011. T Cell and Dendritic Cell Immune Responses to , p 387-396. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch27
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Image of FIGURE 3
FIGURE 3

Cryptococcal MP synergizes with TLR ligands to enhance DC cytokine production. Murine bonemarrowderived DCs were incubated for 24 h with 10 Jig/ml MP; 10 Jig/ml PamCSK (a synthetic bacterial lipoprotein), which activates TLR1/2; 10 Jig/ml polyinosinepolycytidylic acid (pI:C), which activates TLR3; 1 Jig/ml lipopolysaccharide (LPS), which activates TLR4; 10 Jig/ml imiquimod, which activates TLR7/8; and 10 Jig/ml CpG DNA, which activates TLR9. Supernatants were collected and analyzed for TNF-OC by enzymelinked immunosorbent assay. Data represent means ± standard error of four independent experiments, each of which was performed in singlicate. < 0.001 comparing any TLR ligand alone with the TLR ligand plus MP by the twotailed paired t-test. Figure adapted from Dan et al. ( ).

Citation: Wozniak K, Levitz S. 2011. T Cell and Dendritic Cell Immune Responses to , p 387-396. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch27
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Tables

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TABLE 1

Cytokines associated with protective and nonprotective responses to infection

Citation: Wozniak K, Levitz S. 2011. T Cell and Dendritic Cell Immune Responses to , p 387-396. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch27

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