Death of peripheral CD8+ T cells in the absence of MHC class I is Fas-dependent and not blocked by Bcl-xL.
Productive immune responses require an appropriate environment to support peripheral CD8(+) T cell survival. Although 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 Iby 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 overexpression of Bcl-x(L) 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.
D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000502:physiology; D018106:CD28 Antigens / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002460:Cell Line; D053222:Fas Ligand Protein; D006183:H-2 Antigens / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D051020:bcl-X Protein; D019014:fas Receptor / Q000502:physiology*
C494812:Bcl2l1 protein, mouse; D018106:CD28 Antigens; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D006183:H-2 Antigens; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011948:Receptors, Antigen, T-Cell; D051020:bcl-X Protein; D019014:fas Receptor; D018799:Intercellular Adhesion Molecule-1