CD4+ T cells, but not CD8+ T cells, mediate the breaking of tolerance in mixed allogeneic chimeras (B10 + B10.BR-->B10).
Reconstitution of mouse recipients with a mixture of syngeneic plus allogeneic bone marrow (A+B-->A) results in stable mixed lymphohematopoietic chimerism and donor-specific transplantation tolerance. Previously, it was reported that administration of large numbers of unmanipulated host-type splenocytes to neonatal or adult radiation bone marrow chimeras resulted in a loss of chimerism and donor-specific transplantation tolerance. To characterize the phenotype(s) of cells that were responsible for this loss of chimerism, we performed depletion of various subsets of unmanipulated B10 splenocytes prior to infusion into mixed allogeneic chimeras (B10 + B10.BR-->B10). Recipients were followed serially to identify changes in the level of donor chimerism and by in vitro functional assays of tolerance. We report here that CD4+ T cells, but not CD8+ T cells, were sufficient to mediate the loss of donor chimerism. In all recipients in which allogeneic chimerism became undetectable, there was a simultaneous loss of donor-specific transplantation tolerance.
Wren
S M
SM
Department of Surgery, University of Pittsburgh, Pennsylvania 15261.
Hronakes
M L
ML
Ildstad
S T
ST
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016827:CD8 Antigens / Q000032:analysis*; D002678:Chimera; D004306:Dose-Response Relationship, Immunologic; D006183:H-2 Antigens / Q000276:immunology; D007108:Immune Tolerance; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D016827:CD8 Antigens; D006183:H-2 Antigens