Rapamicin associates with a stronger inhibition of donor-recipient mixed lymphocyte reactions among kidney transplants

Rapamicin (Rapa) is a new immunosuppressive drug currently in use for kidney transplantation (KTX). Its mechanism of action is different as compared to calcineurin inhibitors (CNI) action. Rapa does not seems to modulate the transcription of cytokines, contrary to CNI. However, our group reported several significant differences for growth factors synthesis by aspiration biopsy sample cultures. Mixed lymphocyte reactions (MLR) test the indirect and direct antigen presentation and constitute an indication of the strength of the alloimmune response. We tested the influences of Rapa on MLR as compared with CNI. Thirty-two KTX were divided into two groups; group I (n=17) was treated with Rapa, MMF and pred and group II (n=25) was treated with CNI, MMF and pred. No KTX received antibody induction, all were first cadaver KTX. MLR were done between six and twelve months post-KTX, both in donor-recipient (D/R) and third-party-recipient combinations (R/T). MLR were done as classically described and proliferation was evaluated at the end of the 5th day of culture. Donor cells were obtained from donor spleen procured at the time of organ harvesting. Statistics by Kruskal-Wallis ANOVA. No significant differences were observed by comparing the demographic data of D/R pairs from both groups. Serum creatinine were stable during the previous month, at least. No patient suffered an acute rejection before MLR. The absolute results in cpm in I and II were, respectively: I, D/R, 3404 plus or minus 7373 and 5017 plus or minus 6274 (P=0.017); as for R/T, 35998 plus or minus 41544 and 35417 plus or minus 27617, for I and II, respectively (P=0.582). The relative response was for I and II, respectively: 5.7 plus or minus 14.8% and 11.4 plus or minus 14.8% (P=0.003). Our results are the first evidence that Rapa treatment associates with a significant down-regulation of anti-donor response while third-party response was not affected. Whereas some doubts have been raised that CNI may abrogate the development of T regulatory cells, Rapa does not impair their development. Our results may be explained by this different effects which may be of paramount importance for the KTX survival.