Belfrage H, Dohlsten M, Hedlund G, Kalland T
Department of Cell and Molecular Biology, Lund University, Sweden.
Immunology. 1997 Feb;90(2):183-8. doi: 10.1046/j.1365-2567.1997.00030.x.
Administration of staphylococcal enterotoxin A (SEA) to mice induces profound activation, cytokine production and cytotoxic activity of both CD4+ and CD8+ T cells, but subsequently activated cells are deleted or become anergic. This study demonstrates that administration of interleukin-2 (IL-2) can prevent sea-induced hyporesponsiveness in CD8+ cytotoxic T lymphocytes (CTL). Repeated injections with sea every fourth day resulted in severely reduced cytotoxic activity in the spleen, which correlated with a reduced number of sea-responsive T-cell receptor (TCR)-V beta 11+ CD8+ cells. Studies of purified TCR-V beta 11+ CD8+ cells showed that they possessed intact cytotoxic activity per cell compared with cells from mice given a single injection of SEA, indicating that deletion was the main mechanism for the reduced cytotoxic activity. Combined treatment with SEA and IL-2 increased the number of cytotoxic cells in the spleen after each SEA injection and prevented the down-regulation of cytotoxic activity. Increased cytotoxic activity could be related to increased number and proliferation of CD8+ IL-2R alpha + cells, suggesting that administration of IL-2 maintained IL-2 responsiveness among CD8+ cells. Studies of sorted TCR-V beta 11+ CD8+ cells demonstrated that combined treatment with SEA and IL-2 also increased cytotoxic activity per cell compared with treatment with SEA alone. Taken together, IL-2 administration in vivo augmented SEA-induced expansion of T cells as well as the cytotoxic activity per CTL, and prevented SEA-induced cell deletion.
给小鼠注射葡萄球菌肠毒素A（SEA）可诱导CD4+和CD8+ T细胞的深度激活、细胞因子产生及细胞毒性活性，但随后被激活的细胞会被清除或变得无反应性。本研究表明，注射白细胞介素-2（IL-2）可预防SEA诱导的CD8+细胞毒性T淋巴细胞（CTL）反应低下。每四天重复注射SEA会导致脾脏中细胞毒性活性严重降低，这与对SEA有反应的T细胞受体（TCR）-Vβ11+ CD8+细胞数量减少相关。对纯化的TCR-Vβ11+ CD8+细胞的研究表明，与单次注射SEA的小鼠的细胞相比，它们每个细胞都具有完整的细胞毒性活性，表明细胞清除是细胞毒性活性降低的主要机制。SEA和IL-2联合治疗在每次SEA注射后增加了脾脏中细胞毒性细胞的数量，并防止了细胞毒性活性的下调。细胞毒性活性增加可能与CD8+ IL-2Rα+细胞数量增加和增殖有关，提示注射IL-2维持了CD8+细胞中IL-2的反应性。对分选的TCR-Vβ11+ CD8+细胞的研究表明，与单独用SEA治疗相比，SEA和IL-2联合治疗也增加了每个细胞的细胞毒性活性。综上所述，体内注射IL-2增强了SEA诱导的T细胞扩增以及每个CTL的细胞毒性活性，并防止了SEA诱导的细胞清除。
