Differential roles of Mac-1+ cells, and CD4+ and CD8+ T lymphocytes in primary nonfunction and classic rejection of islet allografts.
The high rate of persistent hyperglycemia, termed primary nonfunction, after islet allotransplantation in C57BL/6 mice recipients of B10.BR strain islets, as compared with B10.BR recipients of C57BL/6 islets, led to a series of experiments to determine whether islet allograft primary nonfunction was attributable to technical aspects of the transplant procedure or whether it was a consequence of alloimmunity. Primary nonfunction was prevented by systemic pharmacologic immunosuppression of the host with cyclosporine. Selective immunodepletion of host CD4+ and CD8+ T lymphocytes significantly extended the time of classic rejection but did not significantly affect the rate of primary nonfunction. However, modulation of macrophages by administration to the host of silica completely abolished primary nonfunction. These observations, in conjunction with the immunohistological findings of intense macrophage infiltration in islet allografts from recipients exhibiting persistent post-transplant hyperglycemia, support the hypothesis that primary nonfunction results from a cell-mediated host-immune response of rapid onset that is dependent on macrophages or macrophage byproducts as the main effectors.
Kaufman
D B
DB
Department of Surgery, University of Minnesota Medical School, Minneapolis 55455.
Platt
J L
JL
Rabe
F L
FL
Dunn
D L
DL
Bach
F H
FH
Sutherland
D E
DE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000943:Antigens, Differentiation / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens; D016009:Chi-Square Distribution; D003524:Cyclosporins / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000276:immunology; D006084:Graft Rejection / Q000187:drug effects / Q000276:immunology*; D007124:Immunoenzyme Techniques; D007515:Islets of Langerhans / Q000276:immunology; D016381:Islets of Langerhans Transplantation; D016177:Macrophage-1 Antigen; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens; D003524:Cyclosporins; D016177:Macrophage-1 Antigen; D016028:Receptors, Leukocyte-Adhesion