Presented at:
World Transplant Congress 2006
Boston, MA, TX, July 22-27, 2004

Regulatory cells of donor and recipient phenotypes in donor stem cell infused kidney transplant recipients treated with alemtuzumab

Mathew J, Vallone T, Carreno M, Garcia-Morales R, Rosen A, Gomez C, Blomberg B, Fuller L, Burke GW, Ciancio G, Esquenazi V, Miller J

University of Miami and the VA Medical Center, Miami, FL

Previous studies from our laboratory had shown that kidney transplant recipients who had received perioperative whole donor bone marrow cell (DBMC) infusions developed chimeric cells of both donor and recipient phenotypes that were potent inhibitors of recipient anti-donor immune responses. We have now monitored the presence such regulatory cells in two Alemtuzumab-treated LRD-kidney transplant recipients infused twice (perioperatively and at 3 months post-transplant) with donor hematopoietic stem cells (DHSC).

Specific anti-donor immune responses by MLR, micro-CML and ELISPOT assays for IFN-gamma and granzyme-B producing cells, and for donor and recipient regulatory cells were serially tested.

During the early post-transplant period, the recipients were profoundly depleted of peripheral lymphocytes. When the lymphocyte count gradually increased the recipients were tested again (at 6 months). It was found that the antidonor MLR responses and IFN- producing cell frequencies remained marginally positive while the CTL activities and granzyme-B producing cell frequencies were undetectable. Depletion of cells of donor phenotype from the responding recipient PBL slightly increased the anti-donor MLR and depletion of CD25+ cells significantly increased these responses [Table 1]. More importantly, when pre-transplant cryopreserved and thawed recipient PBL were used as responders in MLR, purified chimeric cells of both donor and recipient phenotypes potently inhibited the (pre-transplant) responses in a dose-dependent and antigen independent manner. Similar results were also observed when the recipients were re-tested likewise at 12 months post-transplantation.

Taken together these results clearly indicated the development of chimeric donor and recipient regulatory cells consequent to Alemtuzumab treatment and DHSC infusion. These cells may induce donor specific unresponsiveness which in turn may facilitate allograft acceptance.

Table 1: Effect of donor and CD25+ cell depletions on the recipients post-transplant proliferative responses to PHA, donor or third party (data shown as stimulation index in a representative of 3 similar experiments)

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