Sfikakis P P, Oglesby R, Sfikakis P, Tsokos G C
Department of Medicine, Uniformed University of the Health Sciences, Bethesda, MD.
Clin Exp Immunol. 1994 Apr;96(1):8-14. doi: 10.1111/j.1365-2249.1994.tb06221.x.
Successful T cell activation via the T cell receptor (TCR)/CD3 complex requires at least one contact-dependent second signal delivered by costimulatory molecules, including the B7/BB1 molecule, that are present on antigen-presenting cells (APC). SLE is characterized by multiple complex lymphocyte abnormalities of undefined molecular origin. It is currently unclear whether an intrinsic defect of T cell or an underlying APC dysfunction is responsible for defective in vitro proliferation of T cells from patients with SLE. We planned the present experiments to ask whether the TCR/CD3-mediated and B7/BB1-costimulated T cell proliferation is normal in these patients. We used enriched T cell populations that were stimulated with an anti-CD3 MoAb in the presence of controlled quantities of functional B7/BB1 antigen. Freshly isolated T cells from 17 SLE patients (10 and seven patients with either active or inactive disease, respectively) and 11 normal individuals were cocultured with irradiated B7/BB1-transfected P815 cells or parental P815 cells in the presence of OKT3 MoAb at optimal and suboptimal concentrations for 2.5-7 days. Normal or SLE T cells responded similarly to stimulation via anti-CD3, in the absence of B7/BB1 antigen. A several-fold increase in T cell proliferation in the presence of B7/BB1 antigen was observed. Proliferation was inhibited in the presence of anti-B7/BB1 MoAb, but not with control MoAbs. Interestingly, dose-response curves and time kinetics of B7/BB1 costimulation were similar in T cells from patients with either active or inactive SLE at the time of study, and normal individuals. In addition, no differences in the IL-2 receptor release by T cells cultured under these conditions were observed between SLE patients and normal individuals. These results demonstrate that CD28 signalling is not intrinsically impaired in patients with SLE; further studies to investigate whether abnormal B7/BB1 expression is involved in the autoimmune process are needed.
通过T细胞受体（TCR）/CD3复合物成功激活T细胞需要共刺激分子传递至少一种接触依赖性第二信号，包括存在于抗原呈递细胞（APC）上的B7/BB1分子。系统性红斑狼疮（SLE）的特征是存在多种分子起源不明的复杂淋巴细胞异常。目前尚不清楚是T细胞的内在缺陷还是潜在的APC功能障碍导致SLE患者T细胞体外增殖缺陷。我们开展了本实验，以探究这些患者中TCR/CD3介导的和B7/BB1共刺激的T细胞增殖是否正常。我们使用了富集的T细胞群体，在可控量的功能性B7/BB1抗原存在的情况下，用抗CD3单克隆抗体进行刺激。将来自17例SLE患者（分别有10例和7例处于活动期或非活动期疾病）和11名正常个体的新鲜分离的T细胞，与经辐照的B7/BB1转染的P815细胞或亲代P815细胞在最佳和次优浓度的OKT3单克隆抗体存在的情况下共培养2.5 - 7天。在没有B7/BB1抗原的情况下，正常或SLE T细胞对通过抗CD3的刺激反应相似。在存在B7/BB1抗原的情况下，观察到T细胞增殖增加了几倍。在存在抗B7/BB1单克隆抗体的情况下增殖受到抑制，但对照单克隆抗体则无此作用。有趣的是，在研究时，活动期或非活动期SLE患者的T细胞与正常个体的T细胞中，B7/BB1共刺激的剂量反应曲线和时间动力学相似。此外，在这些条件下培养的T细胞释放白细胞介素-2受体方面，SLE患者和正常个体之间未观察到差异。这些结果表明，SLE患者的CD28信号传导没有内在受损；需要进一步研究以调查异常的B7/BB1表达是否参与自身免疫过程。
