Microchimerism after liver transplantation: Absence of rejection without abrogation of anti-donor cytotoxic T-lymphocyte–mediated alloreactivity

Abstract

Microchimerism (MC) is defined by the persistence of <1% circulating donor cells resulting from cell migration from the graft; MC may play a role in the induction of unresponsiveness to allogeneic tissues, or may be merely the consequence of the graft's acceptance following immunosuppression. To analyze early MC (7 patients) and late MC (12 patients) following a liver transplantation, we designed a sensitive and semiquantitative nested polymerase chain reaction (PCR) protocol based on the detection of incompatible human leukocyte antigen (HLA)-DRB1 donor alleles. MC was measured in multiple PCR samples and expressed as percent positive PCRs / time point. The detection level was 1 donor cell / 10(5) patient cells. All patients had detectable early MC, ranging from 5 to 100% positive PCRs in the 1st 3 months after transplantation. The kinetic analysis demonstrated that MC decreased during the 1st year in 6 of 7 patients. All of the 4 patients with the lowest MC had rejection episodes, vs. none among the 3 patients with MC >50%. However, cytotoxic T-lymphocyte reactivity (CTL) against HLA class I donor antigens could be demonstrated 1 year posttransplant in 2 patients with a high level of early MC. MC is a dynamic process, which is easily detectable <3 months after liver transplantation. In conclusion, a correlation between the level of early MC and the absence of rejection episodes was observed. However, high levels of early MC did not abrogate the persistence of an alloreactive response measured in vitro 1 year after transplantation, which suggests that MC did not lead to clonal deletion of donor-specific CTL.