IMMUNE REGULATION AND GRAFT SURVIVAL IN KIDNEY TRANSPLANT RECIPIENTS ARE BOTH ENHANCED BY HLA-DR SHARING.

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IMMUNE REGULATION AND GRAFT SURVIVAL IN KIDNEY TRANSPLANT RECIPIENTS ARE BOTH ENHANCED BY HLA-DR SHARING.
D.S. Rodriguez BS , E. Jankowska-Gan MS , L.D. Haynes MS , G. Leverson PhD , D. Heisey PhD and W.J. Burlingham PhD . Madison WI, University of Wisconsin, 53792, Surgery .

Finding a natural mechanism to replace drugs in the maintenance of the allograft would be ideal. Hypothesis: Donor/recipient sharing of the particular HLA required for peptide presentation to the host T reg cell will increase the incidence of immune regulation. Methods: In two retrospective studies, renal transplant (RTx) survival from living related donors (LRD; n=1085) and cadaver donors (cad; n=845) were analyzed using a log rank test. PBMC from RTx recipients (n=62) were injected along with PBS (negative control) or a positive control recall Ag (TT or EBV) into the footpads of SCID mice. Injections of PBMC + donor Ag (dAg; cell sonicate) alone or donor+ recall Ag were done to test for linked-suppression. Swelling was measured 24 hrs later. Results: Matching for HLA-DR was correlated (p=.045) by Cox proportional hazards test with the presence of immune regulation in cad RTx recipients (n=29). Overall, 6/11 patients fully matched for HLA-DR showed a regulated phenotype (low dAg DTH and >50% linked suppression), and none were sensitized (≥20 swelling units vs dAg). In contrast, 2/4 0 DR matched patients were sensitized to dAg and 0/4 were regulators. Remarkably, 100% (7/7) of HLA-identical LRD RTx recipients regulated their minor H-specific anti-donor DTH, consistent with their superior graft survival at 5 yrs compared to 1 haplo matched-LRD (92% vs 76%). Cad RTx fully matched for HLA-DR had a graft survival rate of 80% at 5 yrs, better than 1 DR and 0 DR matched recipients (70%, 58%; p=.0001). Conclusion: HLA-DR sharing correlated with both development of immune regulation and favorable long-term graft outcome. This suggests that the reason for improved survival of class II-matched grafts may be better induction of graft protective CD4+ T reg cells.