Stagg A J, Funauchi M, Knight S C, Webster A D, Farrant J
Antigen Presentation Group, Clinical Research Centre, Harrow, UK.
Clin Exp Immunol. 1994 Apr;96(1):48-53. doi: 10.1111/j.1365-2249.1994.tb06228.x.
Antigen-driven responses by T cells from patients with CVID and normal subjects have been assessed. Low-density cells enriched for antigen-presenting dendritic cells were cultured with T cells using a 20-microliters hanging drop system. T cells from all subgroups of CVID patients showed markedly reduced responses to the recall antigens purified protein derivative (PPD) or tetanus toxoid, whereas responses by cells from patients with X-linked agammaglobulinaemia, used as a disease control, were in the normal range. However, primary allo-stimulation of CVID T cells was normal. CVID cells from two patients failed to respond to stimulation with a neoantigen, an HIV env peptide, under conditions where normal T cells did respond. These data illustrate a profound defect in antigen-stimulated T cell proliferation in vitro in all groups of CVID patients, but do not distinguish whether the defect is in the presenting cell or in the T lymphocyte. In vivo, germinal centre B cells are thought to present antigen to primed T cells to obtain essential signals (e.g. CD40 ligand and IL-2) for B cell survival and progression to immunoglobulin secretion. A failure of antigen-specific T cell function in vivo in CVID would thus not provide the primed T cells needed for B cell rescue, and could be the primary defect leading to the low immunoglobulin production in this condition.
对常见变异型免疫缺陷病（CVID）患者和正常受试者的T细胞的抗原驱动反应进行了评估。使用20微升悬滴系统，将富含抗原呈递树突状细胞的低密度细胞与T细胞一起培养。CVID患者所有亚组的T细胞对回忆抗原纯化蛋白衍生物（PPD）或破伤风类毒素的反应均明显降低，而用作疾病对照的X连锁无丙种球蛋白血症患者的细胞反应在正常范围内。然而，CVID T细胞的初次同种异体刺激是正常的。在正常T细胞有反应的条件下，两名CVID患者的细胞对新抗原HIV env肽的刺激没有反应。这些数据表明，在所有CVID患者组中，体外抗原刺激的T细胞增殖存在严重缺陷，但无法区分缺陷是在呈递细胞还是T淋巴细胞中。在体内，生发中心B细胞被认为将抗原呈递给致敏T细胞，以获得B细胞存活和向免疫球蛋白分泌进展所需的基本信号（如CD40配体和IL-2）。因此，CVID患者体内抗原特异性T细胞功能的缺陷将无法提供B细胞拯救所需的致敏T细胞，并且可能是导致这种情况下免疫球蛋白产生低下的主要缺陷。
