Characterization of apoptosis-resistant antigen-specific T cells in vivo.
Clonal deletion via activation-induced apoptosis (AIA) of antigen-specific T cells (ASTC) plays a very important role in the induction of peripheral tolerance. However, none of the studies performed so far has shown a complete deletion of ASTC, a small population always persisting in the periphery. The mechanism by which this small population of ASTC escapes AIA has not been determined. Since the existence of these ASTC may influence the outcome of autoimmune diseases and long-term graft survival, we have characterized the properties of these residual ASTC in vivo with the objective of determining mechanisms that may contribute to their persistence. It was found that the resistance of the residual ASTC to AIA is not due to lack of activation or Fas/Fas-L expression. Compared to those susceptible to AIA, the residual ASTC express a high level of Th2-type cytokines that may help them to escape from AIA. Furthermore, they are able to suppress proliferation of other ASTC, suggesting they may, in fact, prolong tolerance in vivo.
Zhang
L
L
Department of Cellular and Molecular Pathology, Toronto Hospital Research Institute, University of Toronto, Canada.
Miller
R G
RG
Zhang
J
J
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D003602:Cytotoxicity, Immunologic; D017931:DNA Primers; D005434:Flow Cytometry; D007108:Immune Tolerance; D016219:Immunotherapy, Adoptive; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D008285:Major Histocompatibility Complex; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D019014:fas Receptor / Q000096:biosynthesis
D017931:DNA Primers; D012333:RNA, Messenger; D019014:fas Receptor