Natural killer type 2 bias in remission of multiple sclerosis
Kazuya Takahashi, … , Shuji Hashimoto, Takashi Yamamura
Kazuya Takahashi, … , Shuji Hashimoto, Takashi Yamamura
Published March 1, 2001
Citation Information: J Clin Invest. 2001;107(5):R23-R29. https://doi.org/10.1172/JCI11819.
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Natural killer type 2 bias in remission of multiple sclerosis

Abstract

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-12Rβ2 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.

Authors

Kazuya Takahashi, Sachiko Miyake, Takayuki Kondo, Keiji Terao, Megumi Hatakenaka, Shuji Hashimoto, Takashi Yamamura

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Surface expression of CD95 on NK cells in MS-rem and controls. (a) Frequ...
Surface expression of CD95 on NK cells in MS-rem and controls. (a) Frequency of CD95+ NK cells. Freshly isolated PBMCs were stained with anti–CD3-FITC, anti–CD56-PE, and anti–CD95-biotin/Streptavidin-Cychrome and were analyzed by flow fluorocytometry within 2 hours after drawing blood. The data are expressed as percentages of CD95+ cells among CD56+CD3–-gated NK cells. Controls for MS-rem include HS, patients with other neurological diseases (OND) (Parkinson disease [n = 4], spinocerebellar degeneration [n = 2], amyotrophic lateral sclerosis [n = 1]) and those with other autoimmune diseases (OAI) (thyroiditis [n = 5], myasthenia gravis [n = 1], inflammatory demyelinating polyneuropathy [n = 1]). Kruskal-Wallis test with Scheffe’s F test was used for statistical analysis. Horizontal bars indicate mean values. (b) CD95 expression on NK cells from MS-rem versus HS. PBMCs were stained with anti–CD3-FITC, anti–CD56-PE, and anti–CD95-biotin/Streptavidin-Cychrome. CD56+CD3– lymphocytes were gated and analyzed for CD95 expression versus side scatter. The horizontal bars indicate the fluorescence intensity distinguishing CD95+ and CD95– cells. Shown are representative data out of 20 samples (MS [n = 10], HS [n = 10]) with similar results.