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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Figure 1

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Cytokine production by NK cells in MS and HS. (a) Quantitative RT-PCR fo...
Cytokine production by NK cells in MS and HS. (a) Quantitative RT-PCR for IL-5, IL-12Rβ2, and IFN-γ. Total RNA was isolated from NK cells obtained from patients with MS in remission and healthy subjects (HS). In the Light Cycler quantitative PCR system, the levels of gene expression are expressed by relative values as described in Methods. (b) Quantification of IFN-γ and IL-5 by ELISA. NK cells were isolated from MS in remission or HS and stimulated with PMA/ionomycin in 96-well U-bottom plates (2 × 105/well). The supernatant was collected 24 hours later, and the levels of IFN-γ and IL-5 in the samples were determined by ELISA. Mann-Whitney U test was used for statistical analysis. Horizontal bars indicate the mean values.