[HTML][HTML] Specific elimination of effector memory CD4+ T cells due to enhanced Fas signaling complex formation and association with lipid raft microdomains

M Ramaswamy, AC Cruz, SY Cleland… - Cell Death & …, 2011 - nature.com
M Ramaswamy, AC Cruz, SY Cleland, M Deng, S Price, VK Rao, RM Siegel
Cell Death & Differentiation, 2011nature.com
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 (T EM)), whereas
central memory and activated naïve CD4+ T cells are relatively resistant to both. Sensitivity …
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 (T EM)), whereas central memory and activated naïve CD4+ T cells are relatively resistant to both. Sensitivity of T EM 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 T EM linked to the pathogenesis of a number of autoimmune diseases.
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