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Publication : Fas (CD95) participates in peripheral T cell deletion and associated apoptosis in vivo.

First Author  Mogil RJ Year  1995
Journal  Int Immunol Volume  7
Issue  9 Pages  1451-8
PubMed ID  7495753 Mgi Jnum  J:29424
Mgi Id  MGI:76958 Doi  10.1093/intimm/7.9.1451
Citation  Mogil RJ, et al. (1995) Fas (CD95) participates in peripheral T cell deletion and associated apoptosis in vivo. Int Immunol 7(9):1451-8
abstractText  Following exposure to some types of antigen (superantigens), responsive T cells expand and then decline in numbers, a phenomenon that has been called 'peripheral deletion'. This process may play a role in limiting autoimmune reactions and in the maintenance of immune homeostasis. Here we describe experiments on peripheral deletion in mice carrying the lpr/lpr defect, which has been shown to be due to defective production of the CD95/Fas molecule. Young lpr/lpr mice with no apparent immunologic abnormalities display a defect in bacterial superantigen-induced peripheral deletion. Apoptotic death of the expanded T cell population associated with such peripheral deletion. Apoptotic death of the expanded T cell population associated with such peripheral deletion in normal animals is dramatically reduced in the mutant mice. Further, the levels of Fas on responding cells in normal mice increases and decreases together with increases and decreases in cell numbers, suggesting that cells with the highest levels of Fas are preferentially deleted. These observations are consistent with the known ability of CD95 to transduce a signal leading to apoptosis, and they implicate this signal transduction pathway in peripheral deletion. In contrast, bacterial superantigen-induced deletion of thymocytes appears to be fully functional in these mice, and thus Fas/APO-1 does not appear to be required for this process. Further, antibody ligation of the TCR on activated T cells from normal or young lpr/lpr mice can induce apoptosis and therefore under some circumstances this phenomenon is not dependent upon CD95/Fas. Thus, to avoid autoreactivity and ensure immune homeostasis, several different apoptotic mechanisms exist in peripheral T lymphocytes, only some of which involve Fas.(ABSTRACT TRUNCATED AT 250 WORDS)
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