Kim Kyoung Soo, Jacob Noam, Stohl William
University of Southern California, Keck School of Medicine, Los Angeles, CA 90033, USA.
Clin Immunol. 2003 Sep;108(3):182-9. doi: 10.1016/s1521-6616(03)00167-0.
Microbial superantigens (SAg), including SEB and TSST-1, polyclonally activate T cells belonging to specific TCR BV families. A pathogenic role for SAg in various human diseases has been suggested, but enthusiasm for this view has been tempered by the T cell oligoclonality in these disorders. To assess whether T cell oligoclonality can emerge following protracted SAg stimulation, human PBMC were stimulated with SEB, TSST-1, or anti-CD3 mAb and maintained in culture with exogenous IL-2. Oligoclonality was appreciated by day 14 among CD4(+) and CD8(+) T cells. In addition, mice transgenic for human DR2 and DQ8 were injected weekly with SEB, and splenic CD4(+) and CD8(+) T cells were analyzed for oligoclonality. In mice that received one or three such injections, little-to-no oligoclonality was detected. In contrast, considerable oligoclonality was detected in mice that received eight weekly SEB injections. Many of these T cell oligoclones were identical to "spontaneously" arising oligoclones detected in SEB-naive mice. Thus, T cell oligoclonality can emerge following chronic SAg stimulation. In hosts who have lost tolerance to self Ag, chronic exposure to SAg may preferentially promote expansion of autoreactive T cells and facilitate development of clinical disease.
微生物超抗原（SAg），包括SEB和TSST-1，可多克隆激活属于特定TCR BV家族的T细胞。已有人提出SAg在多种人类疾病中具有致病作用，但这些疾病中T细胞的寡克隆性使人们对这一观点的热情有所降温。为了评估在长期SAg刺激后是否会出现T细胞寡克隆性，用SEB、TSST-1或抗CD3单克隆抗体刺激人外周血单核细胞（PBMC），并在外源性白细胞介素-2存在的情况下进行培养。在第14天时，CD4(+)和CD8(+) T细胞中出现了寡克隆性。此外，每周给转染了人类DR2和DQ8的转基因小鼠注射SEB，并分析脾脏CD4(+)和CD8(+) T细胞的寡克隆性。在接受一次或三次这种注射的小鼠中，几乎检测不到寡克隆性。相比之下，在接受每周一次共八次SEB注射的小鼠中检测到了相当程度的寡克隆性。许多这些T细胞寡克隆与在未接触过SEB的小鼠中“自发”出现的寡克隆相同。因此，在慢性SAg刺激后可出现T细胞寡克隆性。在对自身抗原失去耐受性的宿主中，长期接触SAg可能会优先促进自身反应性T细胞的扩增，并促进临床疾病的发展。
