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首页> 外文期刊>The Journal of Immunology: Official Journal of the American Association of Immunologists >Superantigen-induced human CD4+ helper/killer T cell phenomenon. Selective induction of Th1 helper/killer T cells and application to tumor immunotherapy.
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Superantigen-induced human CD4+ helper/killer T cell phenomenon. Selective induction of Th1 helper/killer T cells and application to tumor immunotherapy.

机译：超抗原诱导的人类CD4 +辅助/杀伤性T细胞现象。 Th1辅助/杀伤T细胞的选择性诱导及其在肿瘤免疫治疗中的应用。

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摘要

Human CD4+ T cells activated with staphylococcal enterotoxin A (SEA) were fractionated by Percoll discontinuous density gradient centrifugation to enrich SEA-reactive CD4+ T cells. The SEA-reactive CD4+ T cells showed significant cytotoxicity, so-called superantigen-dependent cell-mediated cytotoxicity, against SEA-coated class II-positive tumor cells. During lysis of SEA-coated tumor cells, SEA-reactive CD4+ T cells produced high levels of IL-2 and IFN-gamma but not IL-4 in an Ag-specific manner. The skewing of human CD4+ T cells to Th1-type helper/killer T cells was also demonstrated when SEA-reactive CD4+V beta 5.3+ clonal T cells were cultured with SEA, but not with PHA or OKT3 mAb. Interestingly, the generation of SEA-reactive helper/killer T cells was negatively regulated by IL-4, but up-regulated by IL-12. The SEA-reactive CD4+ helper/killer T cells were able to generate from PBMC of tumor patients and could be expanded to 10(9) levels in a 7-day culture. The SEA-reactive CD4+ helper/killer T cells were specifically targeted to c-erbB-2 positive human colon cancer cells using SEA-conjugated-anti-c-erbB-2 mAb. These results initially demonstrated that SEA-activated human CD4+ T cells are a Th1 type of Th cell that has both helper and killer functions which may be useful for adoptive tumor immunotherapy in combination with SEA-conjugated antitumor mAb.
机译：通过Percoll不连续密度梯度离心法分离经葡萄球菌肠毒素A（SEA）激活的人CD4 + T细胞，以富集SEA反应性CD4 + T细胞。 SEA反应性CD4 + T细胞对SEA包被的II类阳性肿瘤细胞表现出显着的细胞毒性，即所谓的超抗原依赖性细胞介导的细胞毒性。在SEA包被的肿瘤细胞裂解期间，SEA反应性CD4 + T细胞以Ag特异性方式产生高水平的IL-2和IFN-γ，但不产生IL-4。当SEA反应性CD4 + V beta 5.3+克隆T细胞与SEA，而不与PHA或OKT3 mAb培养时，也证明了人类CD4 + T细胞向Th1型辅助/杀伤性T细胞的倾斜。有趣的是，SEA反应性辅助/杀伤性T细胞的生成受IL-4负调节，但受IL-12上调。 SEA反应性CD4 +辅助/杀伤性T细胞能够从肿瘤患者的PBMC中产生，并且在7天的培养中可扩展至10（9）水平。使用SEA共轭抗c-erbB-2 mAb将SEA反应性CD4 +辅助/杀伤性T细胞特异性靶向c-erbB-2阳性人结肠癌细胞。这些结果最初证明，SEA激活的人CD4 + T细胞是Th1型Th细胞，具有辅助功能和杀伤功能，可能与SEA偶联的抗肿瘤mAb结合用于过继肿瘤免疫疗法。

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