Donati D, Degiannis D, Raskova J, Raska K
University Diagnostic Laboratories, UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey.
Kidney Int. 1992 Sep;42(3):681-9. doi: 10.1038/ki.1992.335.
We have studied the effects of uremic serum on the activation state and function of normal lymphocytes in vitro, by examining both accessory cell-dependent and accessory cell-independent responses. Uremic serum was obtained from patients on conservative treatment and from the same patients after they have undergone six months of maintenance hemodialysis. Uremic serum inhibited the proliferative responses to mitogens and to recombinant IL-2 (rIL-2) of both peripheral blood mononuclear cells (PBMC) and purified T cell populations. However, the responsiveness to IL-2 of pre-formed lymphoblasts, obtained from both PBMC and purified T cells, in the presence of uremic serum was similar to that obtained in the presence of normal serum, or was even enhanced. Uremic serum did not affect the cellular IL-2 receptor alpha (IL-2R) generation though it inhibited significantly the release of soluble IL-2 receptor (sIL-2R) and the production of IL-2 after mitogenic stimulation. Uremic serum from patients after six months of hemodialysis enhanced, but did not completely restore, proliferative responses and IL-2 production by control PBMC. Neither IL-1 nor IL-2R, which are present at elevated concentrations in uremic serum, appeared to be responsible for serum effects on in vitro responses of control lymphocytes. In conclusion, our results indicate that uremic serum affects both accessory cell-mediated and accessory cell-independent normal T cell responses. Uremic serum inhibition of T cell proliferation is associated with down-regulation of IL-2 synthesis by lymphocytes and the induction of an abnormal state of activation of lymphoblasts which is further enhanced following chronic hemodialysis.
我们通过检测辅助细胞依赖和辅助细胞非依赖反应，研究了尿毒症血清对体外正常淋巴细胞激活状态和功能的影响。尿毒症血清取自接受保守治疗的患者以及这些患者接受六个月维持性血液透析之后。尿毒症血清抑制外周血单个核细胞（PBMC）和纯化T细胞群体对丝裂原和重组白细胞介素-2（rIL-2）的增殖反应。然而，在尿毒症血清存在的情况下，从PBMC和纯化T细胞获得的预先形成的成淋巴细胞对IL-2的反应性与在正常血清存在的情况下获得的反应性相似，甚至有所增强。尿毒症血清不影响细胞白细胞介素-2受体α（IL-2R）的产生，尽管它在丝裂原刺激后显著抑制可溶性IL-2受体（sIL-2R）的释放和IL-2的产生。接受六个月血液透析后的患者的尿毒症血清增强了，但没有完全恢复对照PBMC的增殖反应和IL-2产生。在尿毒症血清中浓度升高的IL-1和IL-2R似乎都不是血清对对照淋巴细胞体外反应产生影响的原因。总之，我们的结果表明，尿毒症血清影响辅助细胞介导和辅助细胞非依赖的正常T细胞反应。尿毒症血清对T细胞增殖的抑制与淋巴细胞IL-2合成的下调以及成淋巴细胞异常激活状态的诱导有关，这种异常激活状态在慢性血液透析后会进一步增强。
