Shutdown of an acute T cell immune response to viral infection is mediated by the proapoptotic Bcl-2 homology 3-only protein Bim.
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.
Pellegrini
Marc
M
Division of Molecular Genetics of Cancer, The Walter and Eliza Hall Institute of Medical Research, Parkville 3050, Australia.
Belz
Gabrielle
G
Bouillet
Philippe
P
Strasser
Andreas
A
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D002455:Cell Division; D005260:Female; D006561:Herpes Simplex / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000302:isolation & purification; D015851:Interleukin-7 / Q000494:pharmacology; D007700:Kinetics; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000276:immunology / Q000473:pathology
D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D002352:Carrier Proteins; D015851:Interleukin-7; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins