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Tolerance after liver transplantation: does it exist and can immunosuppression be withdrawn?

1999; Elsevier BV; Volume: 31; Issue: 6 Linguagem: Inglês

10.1016/s0168-8278(99)80326-2

1600-0641

Stephen M. Riordan, Roger Williams,

Immunotherapy and Immune Responses

It is a well-established maxim of organ transplantation thation that rejection of the allograft will occur unless donors and recipients are matched for transplantation antigens, especially those encoded by the major histocompatibility complex (MHC) (1). Furthermore, exposure of the recipient to mismatched transplantation antigens will result in sensitisation, increasing the potency of alloreactive T cells by at least 100-fold (2) and leading to the even more aggressive rejection of similarly mismatched second-set allografts (1). These rules do not necessarily apply to liver transplantation. As first reported in a porcine model and subsequently recognised in mice and some rat strains, a transplanted liver may be spontaneously accepted without pharmacological immunosuppression even in the face of full MHC mismatching between donor and recipient (3–7). Spontaneous acceptance of a liver graft is followed within days to weeks by the similar acceptance of skin, kidney, heart and other organs of liver donor, but not third party, strain origin (5,7–13). Donor-specific tolerance may occur even in sensitised recipients (3,8,14). In addition, orthotopic liver transplantation (OLT) has been shown to rapidly reverse established rejection of cardiac allografts previously transplanted from the same strain as the liver donor, an effect more potent than that achieved with pharmacological immunosuppression using cyclosporin and with the added advantage of suppressing only anti-donor immunity (11).