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ASSESSMENT OF DONOR SPECIFIC IMMUNE TOLERANCE IN DONOR BONE MARROW CELL (DBMC) INFUSED LRD-KIDNEY TRANSPLANT PATIENTS.
James M. Mathew, PhD, Teresa Vallone, MT, Carmen Gomez, BS,CHT,CHS, Anne Rosen, BSN, Violet Esquenazi, PhD, Gaetano Ciancio, MD, Camillo Ricordi, MD, George W. Burke, MD and Joshua Miller, MD. Miami FL, USA, University of Miami and the VA Medical Center, 33136, Surgery, Division of Transplantation.
Purpose: To monitor the development of donor specific tolerance in LRD-kidney transplant patients who had received perioperative DBMC infusions so as to identify candidates in whom immunosuppression may be reduced or withdrawn.
Methods: Mixed lymphocyte reaction (MLR), cell mediated lympholysis (CML), limiting dilution analysis (LDA) for the estimation of CTL-precursors, Enzyme-linked ImmunoSpot (ELISPOT) assay for interferon-gamma and granzyme-B secreting cells, trans-vivo delayed type hypersensitivity (tv-DTH) and microcytotoxicity assay for panel reactive antibodies (PRA) were performed serially at various intervals in 23 LRD-kidney/DBMC recipients. The patients had 2.5±0.8 HLA mismatch with the donor and follow-up periods of 36-84 months.
Results: The majority of the recipients tested so far showed donor specific unresponsiveness in LDA and/or CML from year one onwards with only 4 recipients still remaining positive. In their MLR responses to the donor, however, many recipients (10/23) were still marginally positive. All the recipients showed strong responses to third party at all times, thus showing the specificity of unresponsiveness to the donor. Most importantly, 5/9 recipients tested in serial studies most recently showed donor specific unresponsiveness in all six assays (MLR, CML, LDA, ELISPOT, tv-DTH and PRA), with the others being positive only in MLR and/or ELISPOT assays.
Conclusions: Donor specific ex vivo unresponsiveness in a combination of these six assays (except for MLR??) might reveal tolerant recipients in whom immunosuppression may be reduced or even withdrawn.