San Segundo D, López-Hoyos M, Fernández-Fresnedo G, Benito M J, Ruiz J C, Benito A, Rodrigo E, Arias M
Servicio de Inmunología, Hospital Universitario Marqués de Valdecilla, Fundación Marqués de Valdecilla-IFIMAV, Santander, Spain.
Transplant Proc. 2008 Nov;40(9):2885-8. doi: 10.1016/j.transproceed.2008.09.043.
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.
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.
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.
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.
辅助性T细胞1（Th1）和辅助性T细胞2（Th2）于数年前被发现。然而，这种二分法已被其他CD4+ T细胞亚群的发现所打破：促炎性白细胞介素（IL）-17产生性T细胞（Th17）和调节性T细胞（Treg）。后者可抑制由Th1、Th2和Th17细胞驱动的免疫反应。IL-6参与Th17的发育，下调Treg的分化。我们的假设是，Th17和Treg之间的失衡会增强肾移植患者的免疫反应。
我们研究了26例终末期肾病（ESRD）患者和10例因先前移植肾功能障碍而等待二次肾移植的患者。我们评估了CD4+CD25+Foxp3+细胞的数量以及Th17细胞的典型白细胞介素IL-17的血清水平。
我们观察到，与ESRD患者相比，先前移植肾功能障碍患者的CD4+CD25+Foxp3+ T细胞数量较少（中位数分别为3.37个/mm3和8.63个/mm3，P = 0.008）。相反，与ESRD患者（1.39 pg/mL，P = 0.036）相比，移植肾功能障碍患者的IL-17血清水平升高（中位数为4.45 pg/mL），这表明等待二次肾移植的患者处于促炎状态。
先前移植产生的新的同种异体反应有利于Th17而非Treg细胞的产生。再次移植患者中Th17细胞活性增强可能会下调Treg细胞，产生有利于排斥下一次移植的促炎环境。
