Specific elimination of effector memory CD4+ T cells due to enhanced Fas signaling complex formation and association with lipid raft microdomains |
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Authors: | Ramaswamy M Cruz A C Cleland S Y Deng M Price S Rao V K Siegel R M |
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Institution: | Immunoregulation Section, Autoimmunity Branch, NIAMS, NIH, Bethesda, MD 20892, USA. |
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Abstract: | Elimination of autoreactive CD4+ T cells through the death receptor Fas/CD95 is an important mechanism of immunological self-tolerance. Fas deficiency results in systemic autoimmunity, yet does not affect the kinetics of T-cell responses to acute antigen exposure or infection. Here we show that Fas and TCR-induced apoptosis are largely restricted to CD4+ T cells with an effector memory phenotype (effector memory T cells (TEM)), whereas central memory and activated naïve CD4+ T cells are relatively resistant to both. Sensitivity of TEM to Fas-induced apoptosis depends on enrichment of Fas in lipid raft microdomains, and is linked to more efficient formation of the Fas death-inducing signaling complex. These results explain how Fas can cull T cells reactive against self-antigens without affecting acute immune responses. This work also identifies Fas-induced apoptosis as a possible immunotherapeutic strategy to eliminate TEM linked to the pathogenesis of a number of autoimmune diseases. |
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Keywords: | Fas death receptors lipid raft microdomains CD4 T cells apoptosis |
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