Takimoto H, Yoshikai Y, Kishihara K, Matsuzaki G, Kuga H, Otani T, Nomoto K
Department of Immunology, Kyushu University, Fukuoka, Japan.
Eur J Immunol. 1990 Mar;20(3):617-21. doi: 10.1002/eji.1830200323.
To determine the molecular mechanisms of T cell stimulation by staphylococcal enterotoxin A (SEA), we examined the expression of T cell receptor (TcR) V beta on the T cells from four strains of mice stimulated in vitro with SEA, using flow cytometric analysis for the number of T cells bearing V beta 3, V beta 6, V beta 8, V beta 11 and RNA blotting analysis for the amount of transcripts of V beta 1, V beta 5 and V beta 12. The number of T cell blasts bearing V beta 1, V beta 3, V beta 1 or V beta 12 were increased in the T cell blasts proliferating in vitro in response to SEA in C57BL/6 mice. In AKR/J mice, which contain few V beta 11- or V beta 12-bearing T cells due to a tolerance to the self-MHC class II IE-antigens, T cells bearing V beta 1 or V beta 3 responded to SEA. SEA enriched only V beta 1-bearing T cells in BALB/c mice carrying Mls-2a which lack Mls-1a-reactive V beta 3-bearing T cells as well as V beta 11- and V beta 12-bearing T cells. In spite of the presence of V beta 1-bearing T cells, C3H/He T cells exhibited a very low responsiveness to SEA. T cell repertoires skewed by clonal deletion of self-reactive T cells may in part account for the different sensitivity to SEA among the different strains. A tolerance to SEA can be established in C57BL/6 mice which have been primed i.v. with SEA and treated i.p. with 200 mg/kg of cyclophosphamide 2 days later. All mature T cells bearing V beta 3 or V beta 11 were virtually abolished in the periphery of tolerant mice. These results suggest that most T cells reactive to SEA bear V beta 1, V beta 3, V beta 11 or V beta 12 and that clonal deletion of mature T cells reactive to SEA may account for the cellular mechanisms for cyclophosphamide-induced tolerance to SEA.
为了确定葡萄球菌肠毒素A(SEA)刺激T细胞的分子机制,我们使用流式细胞术分析携带Vβ3、Vβ6、Vβ8、Vβ11的T细胞数量,并通过RNA印迹分析Vβ1、Vβ5和Vβ12转录本的量,来检测四株小鼠体外经SEA刺激的T细胞上T细胞受体(TcR)Vβ的表达。在C57BL/6小鼠中,体外对SEA增殖反应的T细胞母细胞中,携带Vβ1、Vβ3、Vβ1或Vβ12的T细胞母细胞数量增加。在AKR/J小鼠中,由于对自身MHC II类IE抗原耐受,携带Vβ11或Vβ12的T细胞很少,携带Vβ1或Vβ3的T细胞对SEA有反应。在携带Mls - 2a的BALB/c小鼠中,SEA仅富集携带Vβ1的T细胞,该小鼠缺乏对Mls - 1a有反应的携带Vβ3的T细胞以及携带Vβ11和Vβ12的T细胞。尽管存在携带Vβ1的T细胞,但C3H/He T细胞对SEA的反应性非常低。因自身反应性T细胞的克隆缺失而导致的T细胞库偏差,可能部分解释了不同品系对SEA敏感性的差异。在经静脉注射SEA并用200 mg/kg环磷酰胺腹腔注射处理2天后的C57BL/6小鼠中,可以建立对SEA的耐受性。在耐受小鼠的外周,几乎所有携带Vβ3或Vβ11的成熟T细胞都被清除。这些结果表明,大多数对SEA有反应的T细胞携带Vβ1、Vβ3、Vβ11或Vβ12,并且对SEA有反应的成熟T细胞的克隆缺失可能是环磷酰胺诱导对SEA耐受性的细胞机制。