Presented at:
ASHI 31st Annual Meeting, Washington, DC, October 17-21, 2005.
Regulatory cell development in an LRD-kidney transplant recipient treated with alemtuzumab and donor stem cell infusions (ITN protocol)
Mathew JM, Vallone T, Carreno M, Rosen A, Gomez C, Garcia-Morales R, Blomberg B, Fuller L, Burke G, Ciancio G, Esquenazi V, Miller J
University of Miami , Miami , FL
Our laboratory had previously shown that chimeric cells of both donor and recipient phenotypes were potent inhibitors of recipient anti-donor immune responses in LRD-kidney transplant recipients who had received perioperative whole donor bone marrow cell (DBMC) infusions. We have now analyzed such regulatory cells in an Alemtuzumab-treated LRD-kidney transplant recipient infused twice (perioperatively & 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 tested.
Early post-transplant, the recipient was profoundly depleted of peripheral lymphocytes and unresponsive to the donor, which later became marginal. In vitro depletion of CD25+ cells from responder recipient PBL slightly increased anti-donor MLR (S.I. from 1.5 to 3 & 3.2 to 5 at 12 & 24 weeks, respectively). Similarly, depletion of donor phenotype cells increased the responses which were re-inhibited when the donor cells were added back. When pre-transplant cryopreserved and thawed recipient PBL were used as responders in MLR, purified chimeric cells of both donor and recipient phenotypes (4, 6 & 12 months post-transplant) potently inhibited the (pre-transplant) responses in a dose-dependent manner.
These results clearly indicate (multiple types of) chimeric donor and recipient regulatory cells appear consequent to Alemtuzumab treatment and DHSC infusion. Speculatively, this may facilitate allograft acceptance.