Abstract
We used mutant Fas-deficient (lpr) or Bim-deficient mice to investigate the role of the death receptor and Bcl-2-regulated apoptotic pathways in terminating a physiological T cell response to herpes simplex virus infection. In WT and lpr mice CD8+ antigen-specific T cells were deleted after viral clearance. In contrast, the immune response was not terminated in Bim-deficient mice despite viral clearance, and CD8+ antigen-specific T cells accumulated in the spleen. Thus, Bim is dispensable for viral clearance but is necessary for the death of activated T cells when immune responses are terminated. These findings have implications for the therapeutic manipulation of immune responses to infections and immunization.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis
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Apoptosis Regulatory Proteins
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Bcl-2-Like Protein 11
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / pathology
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Carrier Proteins / genetics
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Carrier Proteins / immunology*
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Cell Division
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Female
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Herpes Simplex / immunology*
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Herpes Simplex / pathology
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Herpes Simplex / virology
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Herpesvirus 1, Human / isolation & purification
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Interleukin-7 / pharmacology
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Kinetics
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Lymph Nodes / immunology
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Lymph Nodes / pathology
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Lymphocyte Activation
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Male
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Membrane Proteins*
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Mice
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Mice, Inbred C57BL
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Mice, Inbred MRL lpr
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Mice, Knockout
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Proto-Oncogene Proteins*
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Recombinant Proteins / pharmacology
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Spleen / immunology
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Spleen / pathology
Substances
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Apoptosis Regulatory Proteins
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BCL2L11 protein, human
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Bcl-2-Like Protein 11
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Bcl2l11 protein, mouse
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Carrier Proteins
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Interleukin-7
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Membrane Proteins
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Proto-Oncogene Proteins
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Recombinant Proteins