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IMMUNOMONITORING IN ALLOGRAFT RECIPIENTS TREATED WITH A T CELL DEPLETING PROTOCOL AND MINIMUM IMMUNOSUPPRESSION.
Carol Bentlejewski, BS, Noriko Murase, MD, Diana Metes, MD, David Guaspari, BS, Angie Farren, BS, Pam McGregor, BS and Adriana Zeevi, PhD. Pittsburgh PA, USA, UPMC, Pathology and Surgery.
We report on immunological and hematological parameters of kidney and liver transplant recipients who received pre-transplant (Tx) Thymoglobulin (THY) or Campath (CAM) and post-Tx tacrolimus monotherapy.
Blood samples were obtained at 1, 3, 6, and 12 mo post-Tx for four-color flow cytometry of leukocyte lineages, in vitro cell proliferation assays, and ELISPOT using donor cells.
Treatment with THY resulted in post-Tx lymphocyte depletion while CAM had a more prolonged impact on lymphocyte recovery. Recovery of CD4 population was slower than CD8 with CD4/CD8 < 0.8 at 6-12mo. DC1 and DC2 populations decreased post-Tx; DC1 recovered by 12 mo (49% vs. 57%) while DC2 recovery was slow (5.5 ± 5.0% vs. 15.0 ± 9.0%). CAM, but not THY, effectively depleted B cells for nearly 12 mo. Detailed in vitro studies (MLR, CML, limiting dilution and ELISPOT) were performed in 20 kidney and 16 liver recipients with >1 yr follow-up. Kidney-Tx on multiple drugs showed global suppression to mitogens and alloantigens, while 2/3 of recipients on spaced weaning showed donor-specific hyporeactivity with vigorous responses to mitogens and 3rd party alloantigens. Kidney-Tx on spaced monotherapy exhibited anti-donor MLR, but had low CTLp frequencies <1:90,000-300,000. Half of the liver-Tx showed donor-specific hyporeactivity or total suppression in MLR and CML. The other half showed reactivity to mitogens and alloantigens in MLR. Donor killing in CML was 8-43% with low CTLp frequencies.
Conclusions: donor-specific immune modulation was observed in a subset of allograft recipients pretreated with THY or CAM. In contrast, patients on continuous multiple drugs showed overall suppression.