Death of peripheral CD8+ T cells in the absence of MHC class I is Fas-dependent and not blocked by Bcl-xL

Mary A. Markiewicz, Ian Elliott Brown, Thomas F. Gajewski

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Productive immune responses require an appropriate environment to support peripheral CD8+ T cell survival. Althoug h host MHC class I molecules appear to be required for this process, the cellular and molecular requirements have not been comprehensively studied. Using adoptive transfer of 2C/recombinase-activating gene-2 (RAG-2 -/- TCR-transgenic T cells, we found that the survival of both naive and effector CD8+ T cells was dependent upon host expression of the same MHC class I alleles that supported thymic selection. Expression of appropriate MHC class I by either bone marrow- or non-bone-marrow-derived cells was sufficient, suggesting that professional antigen-presenting cells were not mandatory. In contrast to MHC class I, neither T cell expression of CD28 nor host expression of ICAM-1 was required for peripheral T cell survival. Finally, T cell death in the absence of appropriate host MHC class I was overcome by elimination of Fas signaling but not by over-expression of Bcl-XL by CD8+ T cells. These results suggest that, in the absence of a survival signal provided by engagement of host MHC/self peptide complexes, CD8+ T cells die via a Fas-dependent, mitochondria-independent pathway.

Original languageEnglish (US)
Pages (from-to)2917-2926
Number of pages10
JournalEuropean Journal of Immunology
Issue number10
StatePublished - Oct 2003
Externally publishedYes


  • Apoptosis
  • CD8
  • MHC
  • T lymphocytes
  • TCR

ASJC Scopus subject areas

  • Immunology


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