Lung allografts are considered to be more immunogenic than other solid organs. Little is known about the effectiveness of immunosuppressive regimens after lung transplantation. Herein, we describe a novel model of murine vascularized orthotopic lung transplantation we used to study the effects of costimulatory blockade on lung rejection. Transplants were performed in the Balb → B6 strain combination. Recipients were either not immunosuppressed or received perioperative CD40/CD40L and CD28/B7 costimulatory blockade. Nonimmunosupressed Balb/c → B6 lung transplants had severe acute rejection 7 days after transplantation and CD8+ T cells outnumbered CD4+ T cells within the allografts. Alternatively, B6 recipients that received perioperative costimulatory blockade had minimal inflammation and there were nearly equal numbers of CD8+ and CD4+ T cells in these grafts. Approximately one third of graft-infiltrating CD4+ T cells expressed Foxp3. CD4+ T cells isolated from these grafts induced apoptosis of alloreactive CD8+ T cells that were stimulated with donor splenocytes in vitro. In contrast with wild-type B6 recipient mice, we observed severe rejection of Balb/c lungs 7 days after transplantation into Bcl-2 transgenic B6 recipients that had received costimulatory blockade. CD8+ T cells outnumbered CD4+ T cells in these immunosuppressed Bcl-2 transgenic recipients and, compared with immunosuppressed wild-type B6 recipients, a lower percentage of graft-infiltrating CD4+ T cells expressed Foxp3, and a higher percentage of graft-infiltrating CD8+ T cells expressed intereferon-γ. Thus, our results show that perioperative blockade of the CD40/CD40L and CD28/B7 costimulatory pathways markedly ameliorates acute rejection of lung allografts in wild type but not Bcl-2 transgenic recipients.
|Number of pages||3|
|Publication status||Published - Jan 1 2009|
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