The roles of costimulation and Fas in T cell apoptosis and peripheral tolerance

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Abstract

Using cells from TCR transgenic mice that do or do not express Fas, we show that there are two mechanistically distinct forms of apoptosis in CD4+ T cells. Naive T cells undergo apoptosis if cultured in the absence of antigen or costimulation. This form of programmed cell death (PCD) is not dependent on Fas, and is prevented by CD28-mediated signals, which lead to the secretion of growth factors and the expression of survival genes, such as bcl-xL. Recently activated T cells undergo apoptotic death upon repeated stimulation. This activation-induced cell death (AICD) is mediated by Fas, but is independent of costimulation and is not prevented by IL-2 or bcl-xL. Finally, we show that peripheral tolerance may be induced in vivo independent of Fas-mediated cell death.

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Van Parijs, L., Ibraghimov, A., & Abbas, A. K. (1996). The roles of costimulation and Fas in T cell apoptosis and peripheral tolerance. Immunity, 4(3), 321–328. https://doi.org/10.1016/S1074-7613(00)80440-9

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