Evidence of Indirect Allorecognition in Long-Term Human Renal Transplantation

The purpose of this study was to investigate indirect alloreactivity in the peripheral blood of long-term renal transplanted patients. We evaluated the T cell proliferative response to a whole pool of donor cell-derived allopeptides, processed and presented by host antigen-presenting cells (APC), rather than to synthetic peptides. For the indirect pathway, proliferation assays were performed using APC-depleted donor cells. Indirect alloreactivity was detected in 57% (8/14) of the patients, 6 of whom presented no evidence of rejection, but 2 patients had a diagnosis of chronic rejection. In 4 of 8 positive cases (50%), proliferation was detected with 5 days of culture, and sometimes indirect alloresponse was the dominant route. We present evidence that the indirect alloproliferative response to a pool of naturally processed donor peptides is present in the peripheral blood of long-term renal transplanted patients irrespective of rejection.