Primate Cardiac Allo- and Xenotransplantation: Modulation of the Immune Response with Photochemotherapy

Abstract

Survival of heterotopic allo- and xenografts was studied in a primate cardiac transplantation model. Initially, animals were presensitized to donor xenoantigens by blood transfusion and treated with strategies designed to elicit pretransplant immunosuppression. These animals underwent rapid rejection whether treated with ciclosporin and conventional immunosuppression, autologous sera, sensitized lymphocytes, or photochemotherapy. In a nonsensitized xenograft study, xenografts were maintained for prolonged periods with a combination of ciclosporin and photochemotherapy. All animals treated with photochemotherapy demonstrated periodic suppression of the mixed leukocyte culture response to their donor. Inhibition of lymphocytotoxic antibody was achieved only in animals treated with both ciclosporin and photochemotherapy. Xenosensitized animals were secondarily exposed to donor alloantigens. These animals were successfully allografted. Ciclosporin therapy was terminated and the animals maintained by photochemotherapy alone. This preliminary trial indicates that a combination of ciclosporin and photochemotherapy may be of value in maintaining concordant xenografts and preventing antibody mediated rejection.

Mechanisms of action of extracorporeal photochemotherapy in the control of GVHD: involvement of dendritic cells

“…Experimentally, photoinactivation of splenocytes with psoralen and UV-A light suppresses the induction of GVHD in mice 4,5 but there are no data on the treatment of GVHD as such. Others studies have shown that infusions of photoinactivated antidonor T cells resulted in a prolonged retention of skin or organ allogeneic grafts, 6,7 suggesting the development of an immune reaction responsible for the downmodulation of allogeneic reactive T-cell function. In vivo production of immunosuppressive cytokines by macrophages or monocytes, following ingestion of apoptotic cells, has been suggested as a general immune effect of ECP.…”

Successful Reversal of Recalcitrant Hepatic Allograft Rejection by Photopheresis

“…20 After this initial success, recent trials in humans have similarly shown the reversal of acute cardiac allograft rejection. 21,22 This range of indications for photopheresis has now been expanded to include prophylactic treatment immediately after heart transplantation [23][24][25] and rescue therapy for severe racalcitrant cardiac allograft rejection.…”

Update on extracorporeal photopheresis in heart and lung transplantation

“…The first reports of ECP in solid-organ rejection appeared in 1989 in animal models of transplantation after the recognition that allograft rejection involves clonal expansion of activated T-cells [18,19]. The expansion in the indications for ECP that ensued in the decade that followed will be discussed below.…”