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

We addressed the question of whether allo-transplantation (Tx) induces brea kdown of tolerance to self-antigens or alteration of the autoreactive T cel l repertoire in humans. The serial variation of T cell autoreactivity was s tudied in the peripheral blood of 12 renal transplant patients, by autologo us limiting dilution assay and autologous mixed lymphocyte reaction. Ten of 12 patients presented a positive response in autologous peripheral blood m ononuclear 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 an alyzed, indicating frequent regulatory control of the autologous response. Quantitative analysis performed in eight patients showed an increase in pre cursor frequency at >1 year post-Tx in five patients. These data indicate t hat autoreactivity increases or develops following Tx, in humans. Post-Tx e vents such as alloreactivity, infections or immunosuppression could interfe re with the balance of autoreactive and regulatory cells, leading to change s in the T cell repertoires to self-antigens and eventually breakdown of se lf-tolerance, Further investigation is needed to elucidate whether post-Tx autoreactivity contributes to rejection, plays a regulatory role over allor eactivity or both, at separate times.