Renal transplant patients show variations in their self-reactive repertoires: a serial study

We addressed the question of whether allo-transplantation (Tx) induces breakdown of tolerance to self-antigens or alteration of the autoreactive T cell repertoire in humans. The serial variation of T cell autoreactivity was studied in the peripheral blood of 12 renal transplant patients, by autologous limiting dilution assay and autologous mixed lymphocyte reaction. Ten of 12 patients presented a positive response in autologous peripheral blood mononuclear cells in the post-Tx period, in contrast to four of 12 patients before Tx (P = 0.038). Multi-hit kinetics was found in 57% of the assays analyzed, indicating frequent regulatory control of the autologous response. Quantitative analysis performed in eight patients showed an increase in precursor frequency at >1 year post-Tx in five patients. These data indicate that autoreactivity increases or develops following Tx, in humans. Post-Tx events such as alloreactivity, infections or immunosuppression could interfere with the balance of autoreactive and regulatory cells, leading to changes in the T cell repertoires to self-antigens and eventually breakdown of self-tolerance. Further investigation is needed to elucidate whether post-Tx autoreactivity contributes to rejection, plays a regulatory role over alloreactivity or both, at separate times.