ASSOCIATION OF CIRCULATING IL-12 AND IL-10-PRODUCING DENDRITIC CELL SUBSETS WITH POSTTRANSPLANT TIME INTERVAL AND DOSE OF IMMUNOSUPPRESSION IN RENAL TRANSPLANT RECIPIENTS

Abstract

P1012 Aims: A domination of circulating plasmacytoid dendritic cells type 2 (DC2) late posttransplant was reported to be associated with good liver graft acceptance. In-vitro, both IL-10-producing myeloid and plasmacytoid DC were shown to polarize T helper cells (Th) into Th2 lymphocytes. We investigated proportions and ratios of circulating DC subpopulations producing IL-12 (IL-12+ DC) or IL-10 (IL-10+ DC) in renal allograft recipients and compared the results with graft function, acute rejection or infection, and daily doses of immunosuppressive drugs. Methods: Intracellular IL-12 or IL-10 content of CD11c+CD83+CD40+ DC was measured in freshly obtained whole blood using four-color fluorescence flow cytometry. Proportions of CD11c+CD83+CD40+IL-12+ and CD11c+CD83+CD40+IL-10+ DC were studied in 25 hospitalized renal transplant recipients without acute rejection or infection during the early posttransplant period (<40 days posttransplant; x±1SD: 11±7 days), 32 symptom-free outpatients with functioning renal transplants (>90 days posttransplant; x±1SD: 2762±2423 days), and 17 healthy controls. Results: Early and late posttransplant renal transplant recipients had significantly lower proportions of IL-12+ DC (early: p=0.001; late: p=0.03) and lower ratios of IL-12+/IL-10+ DC (early: p=0.0001; late: p<0.0001) than healthy controls. Proportions of IL-10+ DC were similar in patients and controls (p=n.s.). Outpatients had higher IL-10+ DC (p=0.0004) and lower IL-12+/IL-10+ DC ratios (p=0.05) than transplant recipients early posttransplant. IL-12+ DC (p=0.002) and IL-10+ DC (p=0.0004) increased with time posttransplant and in association with reductions of the daily doses of cyclosporine (IL-12+ DC: p=0.005; IL-10+ DC: p=0.003), methylprednisolone (IL-12+ DC: p=0.001; IL-10+ DC: p<0.0001) and mycophenolate mofetil (IL-12+ DC: p=0.004; IL-10+ DC: p<0.0001). Conclusion: Transplant recipients exhibit significantly lower proportions of circulating IL-12+ DC than healthy controls. The proportions of IL-12+ DC and IL-10+ DC are associated with time after transplantation and dosage of immunosuppression. IL-10+ DC were found to dominate late posttransplant, and this could be interpreted as an adaptation of the immune system to the graft and might be a useful indicator for lowering the dose of immunosuppression during graft quiescence.