Wen R, Surman S, Blackman M A, Woodland D L
Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Cell Immunol. 1997 Mar 15;176(2):166-72. doi: 10.1006/cimm.1996.1077.
Because of the massive cytokine response elicited by superantigen exposure, it has been suggested that superantigens may act as adjuvants to boost conventional antigen responses. However, most previous studies have shown that in vivo exposure to superantigen suppressed subsequent T cell responses. Here we analyzed the effect of the superantigen Staphylococcal enterotoxin B (SEB) on a concurrent CD4(+) immune response to a conventional antigen, an I-Ab-restricted epitope derived from the same protein (SEB127-142). Heat-inactivated SEB, which had lost all superantigenic activity, was capable of eliciting a strong CD4(+) proliferative T cell response to SEB127-142. In contrast, native SEB was relatively nonimmunogenic, even when administered in association with complete Freund's adjuvant. High doses of native SEB coadministered with heat-inactivated SEB had no effect on the peptide response. However, low doses of native SEB were able to strongly enhance the ability of inactive SEB to prime CD4(+) T cells to SEB127-142. Thus, SEB is not always immunosuppressive, and low doses may actually enhance a concurrent immune response. Also, the contribution of Vbeta8(+)/CD4(+) T cells to peptide reactivity was not affected by the presence of low doses of native SEB, suggesting that the enhanced reactivity was not a Vbeta-specific effect of SEB, but was cytokine-mediated.
由于超抗原暴露引发大量细胞因子反应，有人提出超抗原可能作为佐剂增强传统抗原反应。然而，大多数先前研究表明，体内暴露于超抗原会抑制后续的T细胞反应。在此，我们分析了超抗原葡萄球菌肠毒素B（SEB）对同时发生的针对传统抗原（源自同一蛋白质的I-Ab限制性表位，SEB127-142）的CD4(+)免疫反应的影响。已丧失所有超抗原活性的热灭活SEB能够引发针对SEB127-142的强烈CD4(+)增殖性T细胞反应。相比之下，天然SEB相对无免疫原性，即使与完全弗氏佐剂联合使用也是如此。与热灭活SEB共同给药的高剂量天然SEB对肽反应没有影响。然而，低剂量的天然SEB能够强烈增强无活性SEB启动CD4(+) T细胞对SEB127-142反应的能力。因此，SEB并不总是具有免疫抑制作用，低剂量实际上可能增强同时发生的免疫反应。此外，低剂量天然SEB的存在并不影响Vbeta8(+)/CD4(+) T细胞对肽反应性的贡献，这表明增强的反应性不是SEB的Vbeta特异性效应，而是由细胞因子介导的。
