Department of Immunology, National Institute of Neuroscience, NCNP, Ogawahigashi, Kodaira, Tokyo, Japan.
Int Immunol. 2011 Sep;23(9):529-35. doi: 10.1093/intimm/dxr047. Epub 2011 Jun 28.
Mucosal-associated invariant T (MAIT) cells are innate T cells expressing an invariant Vα7.2-Jα33 T-cell antigen receptor α chain and are enriched in mucosal-associated lymphoid tissues. Although the regulatory role of MAIT cells in experimental autoimmune encephalomyelitis has been determined, their role in multiple sclerosis (MS) has not been elucidated. In the present study, the character of MAIT cells in the peripheral blood of MS patients was analyzed. Compared with healthy controls, the frequency of MAIT cells in peripheral blood was significantly reduced in MS patients in remission and even more profoundly reduced in those with relapse. The frequency of MAIT cells reflected the disease activity, as they were reduced significantly in patients with active disease compared with stable patients, and when blood samples from patients undergoing attack were analyzed 2-3 months later, the frequency significantly increased in parallel with clinical recovery. The frequency of MAIT cells positively correlated with the frequency of CD4(+) invariant NKT cells and of CD56(bright) NK cells in healthy controls but not in MS patients. This suggests the existence of an immune-regulatory link between MAIT cells and these other cell populations with disruption of this cross talk in MS. Moreover, MAIT cells showed a suppressive activity against IFN-γ production by T cells in vitro. This suppression required cell contact but was independent of IL-10, inducible co-stimulator or the presence of B cells. Taken together, these results suggest an immune-regulatory role of MAIT cells in MS through suppression of pathogenic T(h)1 cells.
黏膜相关恒定 T（MAIT）细胞是表达不变的 Vα7.2-Jα33 T 细胞抗原受体α链的固有 T 细胞，并且在黏膜相关淋巴组织中丰富。尽管已经确定 MAIT 细胞在实验性自身免疫性脑脊髓炎中的调节作用，但它们在多发性硬化症（MS）中的作用尚未阐明。在本研究中，分析了 MS 患者外周血中 MAIT 细胞的特征。与健康对照组相比，缓解期 MS 患者外周血中 MAIT 细胞的频率明显降低，甚至在复发患者中降低更为明显。MAIT 细胞的频率反映了疾病的活动度，因为与稳定患者相比，活动期患者的 MAIT 细胞明显减少，并且当分析患者发作时的血液样本 2-3 个月后，频率与临床恢复平行显著增加。MAIT 细胞的频率与健康对照组中 CD4（+）不变 NKT 细胞和 CD56（bright）NK 细胞的频率呈正相关，但在 MS 患者中则不相关。这表明 MAIT 细胞与这些其他细胞群体之间存在免疫调节联系，而这种串扰在 MS 中被破坏。此外，MAIT 细胞在体外对 T 细胞 IFN-γ产生具有抑制活性。这种抑制需要细胞接触，但不依赖于 IL-10、诱导共刺激物或 B 细胞的存在。总之，这些结果表明 MAIT 细胞在 MS 中通过抑制致病性 Th1 细胞发挥免疫调节作用。
