Natural killer type 2 bias in remission of multiple sclerosis
Kazuya Takahashi, Sachiko Miyake, Takayuki Kondo, Keiji Terao, Megumi Hatakenaka, Shuji Hashimoto, Takashi Yamamura
Kazuya Takahashi, Sachiko Miyake, Takayuki Kondo, Keiji Terao, Megumi Hatakenaka, Shuji Hashimoto, Takashi Yamamura
View: Text | PDF
Rapid Publication

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

×

Figure 3

Options: View larger image (or click on image) Download as PowerPoint
Characterization of NK phenotype in the clinical course of MS. (a) Reduc...
Characterization of NK phenotype in the clinical course of MS. (a) Reduction of IL-5 mRNA during relapse. Total RNA was isolated from NK cells and then subjected to quantitative RT-PCR analysis. The data obtained from the same patients at different stages are connected with lines. (b) Decreased frequency of CD95+ NK cells during relapse. Freshly isolated PBMCs were stained with anti–CD3-FITC, anti–CD56-PE, and anti–CD95-biotin/Streptavidin-Cychrome and analyzed by flow fluorocytometry. The data are expressed as percentages of CD95+ cells among CD56+CD3–-gated NK cells. A,BSample pair from the same patient analyzed for these two parameters. Mann-Whitney U test was used for both a and b. (c) Increase of CD95+ NK cells after clinical recovery. The frequency of CD95+ NK cells was determined as performed in b. The first samples were obtained on the day of hospitalization (relapse) before starting injection of 1,000 mg/d of methylprednisolone (steroid pulse) for 3 consecutive days. The second samples were obtained 5–7 days after the start of the pulse therapy (shortly after steroid pulse therapy). The third samples were collected 1 month after the first sampling (1 month after relapse). Bars = SE. Friedman test was used for statistical analysis.