The Role of the CD134-CD134 Ligand Costimulatory Pathway in Alloimmune Responses In Vivo

摘要: The CD134-CD134 ligand (CD134L) costimulatory pathway has been shown to be critical for both T and B cell activation; however, its role in regulating the alloimmune response remains unexplored. Furthermore, interactions with other pathways immunosuppressive agents are unclear. We investigated effect of CD134-CD134L blockade on allograft rejection fully MHC-mismatched rat cardiac skin transplantation models. CD134L alone did not prolong graft survival compared that untreated recipients, combination donor-specific transfusion, cyclosporine, or rapamycin, was less effective than B7 prolonging survival. However, blockade, long-term achieved all recipients (>200 days). Moreover, this synergistic reducing frequency IFN-γ-producing alloreactive lymphocytes inhibiting generation activated/effector lymphocytes. Most impressively, prevented a presensitized model using adoptive transfer primed into athymic heart transplant recipients. In comparison (mean time (MST): 5.3 ± 0.5 days), anti-CD134L mAb modestly prolonged (MST: 14 2.8 days) as CTLA4Ig 21.5 1.7 but grafts were rejected within 24 days. Importantly, combined further significantly 75.3 12.7 expansion and/or persistence primed/effector cells. Our data suggest is responses, especially recall/primed CD28-B7 mediating effector responses during rejection. Understanding mechanisms collaboration between these different important development novel strategies promote