Immune function and regulation

Although Fas is expressed by many tissues and cell types, the expression of FasL is relatively restricted. Both CD8+ and CD4+ T cells, natural killer (NK) cells and lymphokine-activated killer (LAK) cells all express functional FasL and are capable of inducing apoptosis in Fas-expressing target cells. However, in spite of its expression by cytotoxic effector cells, in most instances FasL does not appear to play a critical role in CTL killing. Analysis of perforin gene deficient mice and mice mutated in the Fas pathway (lpr/lpr mice) has indicated that CTL killing of target cells is mediated primarily via the perforin/granzyme pathway. In accordance, mice that are perforin deficient are susceptible to many viral infections, whereas Fas-deficient mice mount a normal immune response to most pathogens.

T cells that recognize self antigens are eliminated primarily in the thymus by the process of negative selection. Interestingly, although Fas is expressed in the thymus and thymic subpopulations are susceptible to Fas-induced apoptosis, Fas docs not appear to play a critical role in thymic T cell deletion. In particular, analysis of lpr/lpr and gld/gld mice has indicated that the Fas/FasL apoptotic pathway is not critical for T cell receptor (TCR) repertoire selection in the thymus. Instead, evidence has accumulated that Fas plays a pivotal role in the inactivation and removal of self reactive T cells in the periphery that have escaped thymic deletion. These peripheral self reactive cells are thought to die through the process

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