Recent studies of tolerant kidney transplant patients have identified increased numbers of circulating B cells expressing an immature/transitional phenotype (IgD⁺CD27^–/IgD⁺CD27^–CD24⁺CD38⁺). Similar frequencies of these immature/transitional B cell populations are observed in patients treated with standard immunosuppression that have stable graft function several years after transplant. We have observed that high levels of terminally differentiated memory CD28^–NKG2D⁺ (TDEM) CD8 T cells in the peripheral blood is a risk factor for graft rejection. The goal of this study was to determine the frequencies of immature/transitional B cells and TDEM CD8 T cells and frequencies of alloreactive T cells in the peripheral blood of 27 patients who have maintained stable primary kidney graft function (14 HLA-identical siblings, 7 deceased donor, 4 maternal, 1 paternal, 1 HLA-mismatched sib donor) their HLA-identical/sib kidney allografts for 30-46 years on low doses of immunosuppression. Mean daily prednisone dose in these 27 recipients was 6.9 +/- 2.7 mg; azathioprine was continued in 8 patients (12.5 – 100mg) and 19 patients had been converted to MMF (500-1500mg). Seven patients also received low dose RAPA, and 1 TAC recently. Antibody staining and flow cytometry analyses of peripheral blood mononuclear cells were performed to determine frequencies of immature/transitional B cells and TDEM CD8 and CD4 T cells, which were converted to absolute numbers. Alloreactivity was tested by culturing aliquots of the peripheral blood mononuclear cells with different allogeneic B cell lines overnight and enumerating numbers of IFN-g- and granzyme B-producing cells by ELISPOT assay. Numbers of immature transitional B cells and TDEM CD8 T cells in the peripheral blood of the 27 patients were similar to or lower than those observed in healthy controls and in recipients with stable transplants for 2-10 years. Numbers of alloreactive T cells producing IFN-g and granzyme B were also similar in the 27 patients and healthy controls. Overall, these studies indicate a state of alloimmune quiescence in a cohort of kidney transplant patients with a primary kidney allograft functioning for 30-46 years, the majority from HLA-identical siblings, but nearly 25% from deceased donors.

CITATION INFORMATION: Brown K, Baldwin W, Poggio E, Braun W, Fairchild R. Alloimmune Quiescence in Recipients with Long-Term Surviving Kidney Grafts. Am J Transplant. 2017;17 (suppl 3).

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