Takahashi K, Miyake S, Kondo T, Terao K, Hatakenaka M, Hashimoto S, Yamamura T
Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
J Clin Invest. 2001 Mar;107(5):R23-9. doi: 10.1172/JCI11819.
Multiple sclerosis (MS) is an autoimmune disease characterized by clinical relapse and remission. Because of the potential role of natural killer (NK) cells in the regulation of autoimmunity, we have examined cytokine profile and surface phenotype of NK cells in the peripheral blood of MS. Here we demonstrate that NK cells in the remission of MS are characterized by a remarkable elevation of IL-5 mRNA and a decreased expression of IL-12Rbeta2 mRNA, as well as a higher expression of CD95. Moreover, the NK cells from MS in remission produced much larger amounts of IL-5 than did those from controls after stimulation with phorbol myristate acetate (PMA) and ionomycin. These features are reminiscent of those of NK type 2 (NK2) cells that can be induced in a condition favoring functional deviation of T cells toward Th2. Remarkably, the NK cells lose the NK2-like property when relapse of MS occurs, but regain it after recovery. We also found that NK2 cells induced in vitro inhibit induction of Th1 cells, suggesting that the NK2-like cells in vivo may also prohibit autoimmune effector T cells. Taken together, it is possible that NK cells play an active role in maintaining the remission of MS.
多发性硬化症（MS）是一种以临床复发和缓解为特征的自身免疫性疾病。由于自然杀伤（NK）细胞在自身免疫调节中的潜在作用，我们检测了MS患者外周血中NK细胞的细胞因子谱和表面表型。在此我们证明，MS缓解期的NK细胞具有IL-5 mRNA显著升高、IL-12Rβ2 mRNA表达降低以及CD95表达较高的特征。此外，与对照组相比，经佛波酯（PMA）和离子霉素刺激后，MS缓解期患者的NK细胞产生的IL-5量要多得多。这些特征让人联想到在有利于T细胞功能偏向Th2的条件下可诱导产生的2型NK（NK2）细胞的特征。值得注意的是，MS复发时NK细胞会失去NK2样特性，但恢复后又会重新获得。我们还发现，体外诱导产生的NK2细胞可抑制Th1细胞的诱导，这表明体内的NK2样细胞也可能抑制自身免疫效应T细胞。综上所述，NK细胞有可能在维持MS缓解中发挥积极作用。
