Demonstration that donor-specific nonresponsiveness in human liver allograft recipients is both rare and transient

Background. The side effects of lifetime immunosuppression are a major cause of morbidity and mortality; however, in the absence of prospective monitoring, immunosuppression withdrawal may lead to graft loss from rejection. To detect and monitor suitable recipients for immunosuppression withdrawal, the authors used an in vitro assay of T-cell function to study 71 long-term liver allograft recipients. Methods. Interleukin-2 secretion by blood mononuclear cells was measured in response to recall antigens, alloantigen (donor and third-party), and phytohemagglutinin. Results. Forty-four recipients were studied at a single time point at least 1 month after transplantation. The majority reacted to all antigens (n = 33), whereas four showed globally reduced or absent responses (n = 4) and six had markedly reduced or absent responses to donor alloantigen in the presence of preserved responses to third-party alloantigen and recall antigens. Four of these donor-nonresponsive recipients were retested 6 to 12 months later, by which time all had redeveloped responses to donor alloantigen. Serial measurements for up to 2 years in a prospective cohort of 27 liver allograft recipients showed only two patients to be consistently donor-nonresponsive posttransplant. Conclusions. Most patients rapidly reacquire vigorous immune responses after liver transplantation, and only a minority are hyporesponsive to donor alloantigen. Donor-specific nonresponsiveness is transient in most patients, and serial monitoring is required to define sustained periods of donor-specific nonresponsiveness. Whether such patients are suitable for immunosuppressive withdrawal is unclear.