Rico Miguel A, Ruiz Sara, Subirá Dolores, Barril Guillermina, Cigarrán Secundino, Castañón Susana, Quiroga Juan A, Selgas Rafael, Carreño Vicente
Fundación para el Estudio de las Hepatitis Virales, Madrid, Spain.
J Med Virol. 2004 Jan;72(1):66-74. doi: 10.1002/jmv.10551.
Patients with chronic renal failure undergoing hemodialysis who are infected with hepatitis C virus (HCV) may test consistently anti-HCV negative. Because CD4(+) T-cells provide help for antibody production virus-specific effector CD4(+) T-cell responses were investigated in relation to anti-HCV positivity in 15 hemodialysis patients grouped according to HCV antibody and viremia. CD4(+) T-cell reactivity was studied in peripheral blood mononuclear cells by standard lymphocyte proliferation assay and phenotypic/functional characterization (cell-surface staining/cytokine secretion) by flow cytometry. HCV-specific CD4(+) T-cell proliferation in viremic hemodialysis patients was weak or absent independently of their anti-HCV status. Virus-specific CD4(+) T-cells displayed a memory phenotype and showed low to undetectable capacity to secrete effector interferon (IFN)-gamma. Impaired activation-induced cytokine secretion appeared to be Th1 (IFN-gamma) but not Th2 (interleukin-4)-directed and was virus-specific as cytomegalovirus responses were preserved. The frequency ex vivo of CD3(+)CD4(+)IFN-gamma(+) T-cells was independent of the HCV antibody status and comparable between viremic (range: 0.08-1.54%) or non-viremic (0.11-3.2%) hemodialysis patients and healthy donors (0.13-1.10%; P = 0.58). The numbers of CD3(+)CD4(+)IFN-gamma(+) T-cells augmented slightly (P = 0.047) in HCV-infected hemodialysis patients but markedly in only one (greater than ninefold) after HCV stimulation. In conclusion, hemodialysis patients show limited HCV-specific effector CD4(+) Th1-cell responses which nonetheless seem unrelated to the anti-HCV status and are not more impaired due to the ongoing hemodialysis.
接受血液透析的慢性肾衰竭患者若感染丙型肝炎病毒（HCV），可能会持续检测出抗-HCV阴性。由于CD4(+) T细胞为抗体产生提供帮助，因此针对15名根据HCV抗体和病毒血症分组的血液透析患者，研究了病毒特异性效应CD4(+) T细胞反应与抗-HCV阳性的关系。通过标准淋巴细胞增殖试验研究外周血单个核细胞中的CD4(+) T细胞反应性，并通过流式细胞术进行表型/功能表征（细胞表面染色/细胞因子分泌）。病毒血症血液透析患者中HCV特异性CD4(+) T细胞增殖微弱或不存在，与他们的抗-HCV状态无关。病毒特异性CD4(+) T细胞表现出记忆表型，分泌效应干扰素（IFN）-γ的能力低至无法检测。激活诱导的细胞因子分泌受损似乎是Th1（IFN-γ）而非Th2（白细胞介素-4）导向的，并且是病毒特异性的，因为巨细胞病毒反应得以保留。CD3(+)CD4(+)IFN-γ(+) T细胞的体外频率与HCV抗体状态无关，在病毒血症（范围：0.08-1.54%）或非病毒血症（0.11-3.2%）的血液透析患者与健康供体（0.13-1.10%；P = 0.58）之间相当。HCV感染的血液透析患者中CD3(+)CD4(+)IFN-γ(+) T细胞数量略有增加（P = 0.047），但在HCV刺激后只有一名患者显著增加（超过九倍）。总之，血液透析患者显示出有限的HCV特异性效应CD4(+) Th1细胞反应，尽管如此，这些反应似乎与抗-HCV状态无关，并且不会因持续的血液透析而受到更严重的损害。
