Apoptosis regulators bim and fas function concurrently to control autoimmunity and CD8(+) T cell contraction

作者：Weant Ashley E; Michalek Ryan D; Khan Islam U; Holbrook Beth C; Willingham Mark C; Grayson Jason M^*

来源：Immunity, 2008, 28(2): 218-230.

DOI：10.1016/j.immuni.2007.12.014

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.

• 出版日期2008-2