Kuroda K, Yagi J, Imanishi K, Yan X J, Li X Y, Fujimaki W, Kato H, Miyoshi-Akiyama T, Kumazawa Y, Abe H, Uchiyama T
Department of Microbiology and Immunology, Tokyo Women's Medical College, Japan.
J Immunol. 1996 Aug 15;157(4):1422-31.
In the present study we investigated the mechanism of deletion of superantigen (sAg)-reactive T cells expanded in sAg-injected mice. In staphylococcal enterotoxin A (SEA)-injected mice, IL-2 activity in serum peaked at 1 to 3 h and the expression of IL-2R alpha-chain (IL-2R alpha) on SEA-reactive (V beta 3+, or V beta 11+) T cells peaked at 6 to 12 h after the injection. Expansion of V beta 3+ or V beta 11+ T cells peaked at 2 days after the injection when most of these T cells were IL-2R alpha negative, and IL-2 activity was not detected at all in serum, suggesting the involvement of IL-2 deprivation in the deletion of expanded T cells. Implantation of an osmotic pump containing human rIL-2 (IL-2 pump) prolonged the expanded states of V beta 3+ or V beta 11+ T cells in SEA-injected C57BL/6 mice and of V beta 8+ T cells in SEB-injected MRL +/+ and Fas Ag-defective MRL-Ipr/Ipr mice. Adult thymectomy did not change at all the effect induced by implantation of IL-2 pump. DNA fragmentation was blocked substantially in mice co-treated with SEA and IL-2 pump. In addition, CD4+ T cell blasts, obtained by in vitro stimulation with rIL-2 of splenic CD4+ T cells from mice co-treated with SEA and IL-2 pump, produced substantial amounts of IL-2 upon restimulation with SEA. These results indicate that deprivation of IL-2 is deeply involved in the deletion of expanded sAg-reactive T cells and their anergy induction in sAg-injected mice.
在本研究中，我们调查了在注射超抗原（sAg）的小鼠中扩增的sAg反应性T细胞的缺失机制。在注射葡萄球菌肠毒素A（SEA）的小鼠中，血清中的IL-2活性在1至3小时达到峰值，SEA反应性（Vβ3 +或Vβ11 +）T细胞上IL-2Rα链（IL-2Rα）的表达在注射后6至12小时达到峰值。Vβ3 +或Vβ11 + T细胞的扩增在注射后2天达到峰值，此时这些T细胞中的大多数为IL-2Rα阴性，并且在血清中完全未检测到IL-2活性，这表明IL-2剥夺参与了扩增的T细胞的缺失。植入含有人重组IL-2的渗透泵（IL-2泵）可延长SEA注射的C57BL / 6小鼠中Vβ3 +或Vβ11 + T细胞以及SEB注射的MRL + / +和Fas抗原缺陷型MRL-Ipr / Ipr小鼠中Vβ8 + T细胞的扩增状态。成年胸腺切除术对植入IL-2泵所诱导的效应完全没有影响。在用SEA和IL-2泵共同处理的小鼠中，DNA片段化被显著阻断。此外，通过用rIL-2体外刺激来自用SEA和IL-2泵共同处理的小鼠的脾CD4 + T细胞而获得的CD4 + T细胞母细胞，在用SEA再次刺激时产生大量IL-2。这些结果表明，IL-2剥夺在注射sAg的小鼠中扩增的sAg反应性T细胞的缺失及其无反应性诱导中起重要作用。
