INTRODUCTION: The T(H)1 and T(H)2 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(H)17) and regulatory T cells (Tregs). The latter group inhibits the immune responses driven by T(H)1, T(H)2, and T(H)17 cells. IL-6 is involved in T(H)17 development, down-regulating Treg differentiation. Our hypothesis suggested that an imbalance between T(H)17 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(H)17 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(H)17 instead of Treg cells. The enhanced activity of T(H)17 cells in retransplanted patients may down-regulate Treg cells, producing a proinflammatory environment that favors rejection of the next transplant.
INTRODUCTION: The T(H)1 and T(H)2 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(H)17) and regulatory T cells (Tregs). The latter group inhibits the immune responses driven by T(H)1, T(H)2, and T(H)17 cells. IL-6 is involved in T(H)17 development, down-regulating Treg differentiation. Our hypothesis suggested that an imbalance between T(H)17 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(H)17 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 ESRDpatients (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(H)17 instead of Treg cells. The enhanced activity of T(H)17 cells in retransplanted patients may down-regulate Treg cells, producing a proinflammatory environment that favors rejection of the next transplant.
Authors: Byung Ha Chung; Hye Jwa Oh; Shang Guo Piao; In O Sun; Seok Hui Kang; Sun Ryoung Choi; Hoon Suk Park; Bum Soon Choi; Yeong Jin Choi; Cheol Whee Park; Yong Soo Kim; Mi La Cho; Chul Woo Yang Journal: Exp Mol Med Date: 2011-11-30 Impact factor: 8.718