Journal
IMMUNITY
Volume 28, Issue 2, Pages 218-230Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2007.12.014
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Funding
- NIAID NIH HHS [T32 AI 07401] Funding Source: Medline
- NIAMS NIH HHS [R01 AR 039501] Funding Source: Medline
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Throughout most of adult life, lymphocyte number remains constant because of a balance of proliferation and apoptosis. Mutation of Bim, a proapoptotic protein in the intrinsic death pathway, or Fas, a tumor necrosis factor receptor (TNFR) superfamily member of the extrinsic pathway, results in late-onset autoimmunity and increased antigen-specific CD8(+) T cell responses during viral infection. However, virus-specific immune responses eventually return to amounts comparable to those for nonmutant mice. Here, we show that loss of both Bim and Fas function resulted in a synergistic disruption of lymphoid homeostasis, rapid-onset autoimmunity, and organ-specific blocks on contraction of antiviral immune responses. When lymphocytic choriomeningitis virus (LCMV)-specific immune responses were quantitated, double-mutant mice had 100-fold more antigen-specific memory CD8(+) T cells in their lymph nodes than wild-type mice. Our results demonstrate that multiple death pathways function concurrently to prevent autoimmunity and downsize T cell responses.
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