Thon V, Wolf H M, Sasgary M, Litzman J, Samstag A, Hauber I, Lokaj J, Eibl M M
Institute of Immunology, University of Vienna, Austria.
Clin Exp Immunol. 1997 Nov;110(2):174-81. doi: 10.1111/j.1365-2249.1997.tb08314.x.
CVID is characterized by hypogammaglobulinaemia and impaired antibody production. Previous studies demonstrated defects at the T cell level. In the present study the response of purified CD4+ and CD8+ T lymphocytes to stimulation with anti-TCR monoclonal antibody (the first signal) in combination with anti-CD4 or anti-CD8, anti-CD2 and anti-CD28 MoAbs (the costimulatory signals) was investigated. Both CD4+ and CD8+ T cells from the patients showed significantly reduced IL-2 release following stimulation via TCR and costimulation via CD4 or CD8 and CD2, respectively. However, normal IL-2 production following TCR plus phorbol myristate acetate (PMA) costimulation and normal expression of an early activation marker, CD69, after TCR+CD28 stimulation indicated that TCR was able to transduce a signal. Furthermore, both IL-2 and IL-4 release were impaired in CD4+ lymphocytes following TCR+CD28 stimulation. In addition, stimulation via TCR+CD28 resulted in significantly decreased expression of CD40 ligand in the patients. These results suggest that the integration of activating signals derived from the TCR and costimulatory molecules is defective in CVID patients; the defect is not confined to costimulation via a single molecule, or restricted to cells producing Th1-type cytokines such as IL-2, and is expressed in both CD4+ and CD8+ T cell subsets.
常见变异型免疫缺陷病（CVID）的特征为低丙种球蛋白血症和抗体产生受损。既往研究显示T细胞水平存在缺陷。在本研究中，对纯化的CD4⁺和CD8⁺T淋巴细胞在抗TCR单克隆抗体（第一信号）与抗CD4或抗CD8、抗CD2及抗CD28单克隆抗体（共刺激信号）联合刺激下的反应进行了研究。患者的CD4⁺和CD8⁺T细胞在分别通过TCR刺激以及通过CD4或CD8和CD2共刺激后，IL-2释放均显著减少。然而，TCR加佛波酯肉豆蔻酸酯（PMA）共刺激后IL-2产生正常，且TCR + CD28刺激后早期激活标志物CD69表达正常，这表明TCR能够转导信号。此外，TCR + CD28刺激后，CD4⁺淋巴细胞中IL-2和IL-4释放均受损。另外，TCR + CD28刺激导致患者中CD40配体表达显著降低。这些结果提示，CVID患者中源自TCR和共刺激分子的激活信号整合存在缺陷；该缺陷并不局限于通过单一分子的共刺激，也不限于产生Th1型细胞因子如IL-2的细胞，且在CD4⁺和CD8⁺T细胞亚群中均有表现。
