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

Rona J. Mogil, Laszlo Radvanyi, Rosana Gonzalez-quintial, Richard Miller, Gordon Mills, Argyrios N. Theofilopoulos, Douglas R. Green

Research output: Contribution to journalArticlepeer-review

134 Scopus citations

Abstract

Following exposure to some types of antigen (superantlgens), 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 Ipr/lpr defect, which has been shown to be due to defective production of the CD95/Fas molecule. Young Ipr/lpr mice with no apparent Immunologlc abnormalities display a defect in bacterial superantlgen-induced 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 ligatlon of the TCR on activated T cells from normal or young Ipr/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. Defects in one or more of these mechanisms may have profound deleterious consequences.

Original languageEnglish (US)
Pages (from-to)1451-1458
Number of pages8
JournalInternational Immunology
Volume7
Issue number9
DOIs
StatePublished - Sep 1995
Externally publishedYes

Keywords

  • CD95
  • Fas
  • Immune tolerance
  • Negative selection
  • Superantigen

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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