Abstract
In this study, we investigated the role of TRAIL in Ag-specific CD8 T cell homeostasis after viral infection. TRAIL deficiency does not influence the kinetics of the Ag-specific CD8 T cell responses, and CD8 T cells in TRAIL-deficient mice were able to expand, contract, and generate functional memory cell numbers that were indistinguishable from TRAIL-sufficient wild-type CD8 T cells after acute lymphocytic choriomeningitis virus infection. Interestingly, the ability of "helpless" CD8 T cells to retain their memory phenotypic and functional (i.e., secondary expansion) characteristics was prolonged in TRAIL-deficient mice compared with wild-type CD4-depleted controls. However, TRAIL deficiency only delayed, but did not prevent, the eventual erosion in the quality of helpless memory CD8 T cells, and that correlated with their inability to respond to a second round of Ag-driven proliferation. These data, which suggest that CD4 help consists of both TRAIL-dependent and -independent components, may help to resolve the current controversy between the early programming and maintenance models that were put forward to explain the role of CD4 T cell help in Ag-specific CD8 T cell homeostasis.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis Regulatory Proteins / deficiency*
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Apoptosis Regulatory Proteins / genetics*
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Apoptosis Regulatory Proteins / physiology
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / pathology*
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CD8-Positive T-Lymphocytes / virology
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cell Proliferation
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Epitopes, T-Lymphocyte / immunology
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Homeostasis / genetics
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Homeostasis / immunology
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Immunologic Memory / genetics*
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Immunologic Memory / immunology
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Immunophenotyping
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Lymphocyte Depletion
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Lymphocytic Choriomeningitis / immunology
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Lymphocytic Choriomeningitis / metabolism
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Lymphocytic Choriomeningitis / pathology
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Lymphocytic choriomeningitis virus / immunology
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Membrane Glycoproteins / deficiency*
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Membrane Glycoproteins / genetics*
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Membrane Glycoproteins / physiology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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T-Lymphocytes, Helper-Inducer / cytology
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T-Lymphocytes, Helper-Inducer / immunology
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T-Lymphocytes, Helper-Inducer / metabolism
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TNF-Related Apoptosis-Inducing Ligand
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Time Factors
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Tumor Necrosis Factor-alpha / deficiency*
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Tumor Necrosis Factor-alpha / genetics*
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Tumor Necrosis Factor-alpha / physiology
Substances
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Apoptosis Regulatory Proteins
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Epitopes, T-Lymphocyte
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Membrane Glycoproteins
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TNF-Related Apoptosis-Inducing Ligand
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Tnfsf10 protein, mouse
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Tumor Necrosis Factor-alpha