T cell subsets mediating rejection of established fetal pancreas grafts and failure to observe graft adaptation.
The present study has attempted to elucidate the cellular mechanisms by which long-term established fetal pancreas allografts are rejected. We used an experimental model in which H-2b nude mice were made hyperglycemic by streptozotocin treatment and then engrafted with allogeneic fetal pancreas grafts. These grafts were functional in that engrafted animals returned to near normoglycemia while all animals left unengrafted subsequently died. The fetal pancreas grafts were allowed to reside in the immunoincompetent nude host for 6-9 months prior to T cell reconstitution, at which time animals were reconstituted with either negatively selected CD4+ or CD8+ H-2b T cell subpopulations. We found that a 6-9 month residence in an immunoincompetent host did not lead to a change in the immunogenicity of fetal pancreatic grafts in that both CD4+ and CD8+ T cell subsets were capable of rejecting these long-term established fetal pancreas grafts. The finding that isolated CD8+ spleen T cell subpopulations, which are only activated by antigen-presenting cells of donor origin bearing MHC class I alloantigen, were capable of effecting graft rejection suggested that APC of donor origin persisted in these long-term fetal pancreas allografts.
Rees
M A
MA
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Rosenberg
A S
AS
Singer
A
A
D000222:Adaptation, Physiological / Q000276:immunology; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology*; D016827:CD8 Antigens; D005333:Fetus; D006084:Graft Rejection / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D016035:Pancreas Transplantation / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens