T H17 Versus Treg Cells in Renal Transplant Candidates: Effect of a Previous Transplant

Abstract

Introduction The T H1 and T H2 cells were described several years ago. However, this dichotomy has been disrupted by the description of other CD4 + T cell subsets: the proinflammatory interleukin (IL)-17-producing T cells (T H17) and regulatory T cells (Tregs). The latter group inhibits the immune responses driven by T H1, T H2, and T H17 cells. IL-6 is involved in T H17 development, down-regulating Treg differentiation. Our hypothesis suggested that an imbalance between T H17 and Tregs enhances immune responses among renal transplant patients. Materials and methods We studied 26 end-stage renal disease (ESRD) subjects and 10 patients awaiting a second renal transplant after previous graft dysfunction. We assessed the number of CD4 +CD25 +Foxp3 + cells and serum levels of IL-17, the prototypic interleukin of T H17 cells. Results We observed a lower number of CD4 +CD25 +Foxp3 + T cells among patients with previous graft dysfunction than those with ESRD (median 3.37 vs 8.63 cells/mm 3, P = .008). In contrast, IL-17 serum levels were augmented in graft dysfunction (median 4.45 pg/mL) compared with ESRD patients (1.39 pg/mL, P = .036), suggesting a proinflammatory state in patients awaiting a second renal transplant. Conclusion The emerging alloresponse from a previous transplant favors the generation of T H17 instead of Treg cells. The enhanced activity of T H17 cells in retransplanted patients may down-regulate Treg cells, producing a proinflammatory environment that favors rejection of the next transplant.