Jiang H, Kashleva H, Xu L X, Forman J, Flaherty L, Pernis B, Braunstein N S, Chess L
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4533-7. doi: 10.1073/pnas.95.8.4533.
Vaccination of mice with activated autoantigen-reactive CD4(+) T cells (T cell vaccination, TCV) has been shown to induce protection from the subsequent induction of a variety of experimental autoimmune diseases, including experimental allergic encephalomyelitis (EAE). Although the mechanisms involved in TCV-mediated protection are not completely known, there is some evidence that TCV induces CD8(+) regulatory T cells that are specific for pathogenic CD4(+) T cells. Previously, we demonstrated that, after superantigen administration in vivo, CD8(+) T cells emerge that preferentially lyse and regulate activated autologous CD4(+) T cells in a T cell receptor (TCR) Vbeta-specific manner. This TCR Vbeta-specific regulation is not observed in beta2-microglobulin-deficient mice and is inhibited, in vitro, by antibody to Qa-1. We now show that similar Vbeta8-specific Qa-1-restricted CD8(+) T cells are also induced by TCV with activated CD4(+) Vbeta8(+) T cells. These CD8(+) T cells specifically lyse murine or human transfectants coexpressing Qa-1 and murine TCR Vbeta8. Further, CD8(+) T cell hybridoma clones generated from B10.PL mice vaccinated with a myelin basic protein-specific CD4(+)Vbeta8(+) T cell clone specifically recognize other CD4(+) T cells and T cell tumors that express Vbeta8 and the syngeneic Qa-1(a) but not the allogeneic Qa-1(b) molecule. Thus, Vbeta-specific Qa-1-restricted CD8(+) T cells are induced by activated CD4(+) T cells. We suggest that these CD8(+) T cells may function to specifically regulate activated CD4(+) T cells during immune responses.
用活化的自身抗原反应性CD4(+) T细胞对小鼠进行疫苗接种（T细胞疫苗接种，TCV）已被证明可诱导对随后诱发的多种实验性自身免疫疾病的保护作用，包括实验性变应性脑脊髓炎（EAE）。尽管TCV介导的保护作用所涉及的机制尚不完全清楚，但有证据表明TCV可诱导对致病性CD4(+) T细胞具有特异性的CD8(+)调节性T细胞。以前，我们证明，在体内给予超抗原后，会出现CD8(+) T细胞，它们以T细胞受体（TCR）Vβ特异性方式优先裂解并调节活化的自体CD4(+) T细胞。在β2-微球蛋白缺陷小鼠中未观察到这种TCR Vβ特异性调节，并且在体外被抗Qa-1抗体抑制。我们现在表明，用活化的CD4(+) Vβ8(+) T细胞进行TCV也可诱导类似的Vβ8特异性Qa-1限制性CD8(+) T细胞。这些CD8(+) T细胞特异性裂解共表达Qa-1和小鼠TCR Vβ8的鼠或人转染细胞。此外，用髓鞘碱性蛋白特异性CD4(+)Vβ8(+) T细胞克隆接种的B10.PL小鼠产生的CD8(+) T细胞杂交瘤克隆可特异性识别其他表达Vβ8和同基因Qa-1(a)但不表达异基因Qa-1(b)分子的CD4(+) T细胞和T细胞肿瘤。因此，活化的CD4(+) T细胞可诱导Vβ特异性Qa-1限制性CD8(+) T细胞。我们认为，这些CD8(+) T细胞可能在免疫反应过程中特异性调节活化的CD4(+) T细胞的功能。
