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• W2023854069 abstract "1022 Blockade of T cell costimulatory pathways is an exciting treatment strategy to promote allograft acceptance. The purpose of this study was to explore the role of the CD40 and CD28 costimulatory pathways on allograft rejection mediated by CD4 and CD8 T cell subsets. To investigate the role of B7 interactions on skin allograft rejection, we transplanted Balb/c skin allografts onto T cell deficient B6 RAG 1−/− mice. Recipient mice were reconstituted on the day of transplantation with CD4 or CD8 T cell subsets from B6 wild type. Recipients were left untreated (control) or treated with CTLA4-Ig for 6 days postoperatively. Untreated recipients reconstituted with wild type CD4 or CD8 cells promptly rejected skin allografts (MST 13d, 15d respectively), demonstrating that either cell subset alone is sufficient for prompt rejection in this model. Interestingly, treatment with CTLA4-Ig did not delay CD4 (MST 15d) or CD8 (MST 19d) mediated rejection. Thus, B7 interactions are not critical for CD4 or CD8 mediated skin allograft rejection in this model. To investigate the role of the CD40 pathway on skin allograft rejection, we reconstituted B6 RAG 1−/− recipients of Balb/c skin grafts with T cell subsets from B6 wild type or CD40L−/− mice. Recipient RAG 1−/− mice reconstituted with wild type CD4 or CD8 cells rapidly rejected Balb/c skin allografts (MST 12d, 14d respectively). In contrast, recipients reconstituted with CD40L−/− CD4 or CD8 cells had prolonged allograft survival (MST 56d, 20d respectively). Thus, the CD40 pathway plays a crucial role in acute skin allograft rejection mediated by CD4 cells, and may play some lesser role in allograft rejection mediated by CD8 cells. To further investigate the role of the CD40 pathway on allograft rejection, we reconstituted B6 RAG 1−/− recipients of Balb/c vascularized heart allografts with CD4 or CD8 T cell subsets from B6 wild type or CD40L−/− mice. Cardiac allografts were harvested 7 days after transplantation and analyzed for CD4 or CD8 cell infiltrate by immunohistochemistry. Recipient RAG 1−/− mice reconstituted with wild type CD4 or CD8 cells had a dense infiltration of transferred cells throughout the myocardium, whereas mice reconstituted with CD40L−/− CD4 or CD8 cells had a significant reduction of graft infiltrating T cells. These data demonstrate that in cardiac and skin allograft models, absence of CD40/CD40L interactions reduces both CD4 and CD8 T cell rejection responses." @default.
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• W2023854069 title "Analysis of the CD40 and CD28 T cell Costimulatory Pathways in Allograft Rejection Mediated by CD4 and CD8 T cell Subsets" @default.
• W2023854069 doi "https://doi.org/10.1097/00007890-199904150-01046" @default.
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