Observational support for an immunoregulatory role of CD3+CD4+CD25+IFN‐γ+ blood lymphocytes in kidney transplant recipients with good long‐term graft …

V Daniel, C Naujokat, M Sadeghi… - Transplant …, 2008 - Wiley Online Library
V Daniel, C Naujokat, M Sadeghi, R Weimer, F Renner, S Yildiz, G Opelz
Transplant International, 2008Wiley Online Library
There is evidence that interferon‐gamma (IFN‐γ)‐dependent interactions of dendritic cell
(DC), T regulatory (Treg), and T suppressor (Ts) subpopulations contribute to allograft
acceptance. We measured DC subsets, CD3+ CD4+ CD25+ (Treg phenotype) and CD3+
CD8+ CD28−(Ts phenotype) peripheral blood lymphocytes (PBL) expressing Foxp3, Th1 or
Th2 cytokines, peripheral T‐and B‐cell counts, and plasma cytokines in 33 kidney transplant
recipients with a serum creatinine of≤ 1.8 mg/dl and 32 recipients with a serum creatinine …
Summary
There is evidence that interferon‐gamma (IFN‐γ)‐dependent interactions of dendritic cell (DC), T regulatory (Treg), and T suppressor (Ts) subpopulations contribute to allograft acceptance. We measured DC subsets, CD3+CD4+CD25+ (Treg phenotype) and CD3+CD8+CD28 (Ts phenotype) peripheral blood lymphocytes (PBL) expressing Foxp3, Th1 or Th2 cytokines, peripheral T‐ and B‐cell counts, and plasma cytokines in 33 kidney transplant recipients with a serum creatinine of ≤1.8 mg/dl and 32 recipients with a serum creatinine of ≥2.0 mg/dl more than 100 days post‐transplant. Cell subsets were measured in whole blood using four‐color flow cytometry. Patients with increased creatinine had less frequently detectable CD3+CD4+CD25+IFN‐γ+ PBL than patients with good graft function (P = 0.017). In patients with good graft function, CD3+CD4+CD25+IFN‐γ+ PBL were associated with high Foxp3+, IL‐2+, IL‐12+, IL‐4+, and IL‐10+ CD3+CD4+CD25+ T PBL (P < 0.001), low CD3+CD8+CD28Foxp3+ (P = 0.002), CD3+CD4+DR+ (P = 0.002), CD3+CD8+DR+ T (P = 0.005) and CD19+ B PBL (P = 0.005), and low lineageHLA‐DR+CD11c+CD123 DC1 (P = 0.006). Patients with impaired graft function did not show these associations. Additional flow cytometric analysis confirmed strong co‐expression of IFN‐γ and Foxp3 by CD4+CD25+ PBL particularly in patients with good graft function. Our data support an immunoregulatory role of CD3+CD4+CD25+Foxp3+IFN‐γ+ cells in a subgroup of transplant recipients with good graft acceptance.
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