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Regulation of experimental autoimmune encephalomyelitis by natural killer (NK) cells.

Zhang B, Yamamura T, Kondo T, Fujiwara M, Tabira T - J. Exp. Med. (1997)

Bottom Line: The disease enhancement was associated with augmentation of T cell proliferation and production of Th1 cytokines in response to MOG35-55.We further showed that NK cells inhibit T cell proliferation triggered by antigen or cytokine stimulation.Taken together, we conclude that NK cells are an important regulator for EAE in both induction and effector phases.

View Article: PubMed Central - PubMed

Affiliation: Department of Demyelinating Disease and Aging, National Institute of Neuroscience, Tokyo, Japan.

ABSTRACT
In this report, we establish a regulatory role of natural killer (NK) cells in experimental autoimmune encephalomyelitis (EAE), a prototype T helper cell type 1 (Th1)-mediated disease. Active sensitization of C57BL/6 (B6) mice with the myelin oligodendrocyte glycoprotein (MOG)35-55 peptide induces a mild form of monophasic EAE. When mice were deprived of NK cells by antibody treatment before immunization, they developed a more serious form of EAE associated with relapse. Aggravation of EAE by NK cell deletion was also seen in beta 2-microglobulin-/- (beta 2m-/-) mice, indicating that NK cells can play a regulatory role in a manner independent of CD8+ T cells or NK1.1+ T cells (NK-T cells). The disease enhancement was associated with augmentation of T cell proliferation and production of Th1 cytokines in response to MOG35-55. EAE passively induced by the MOG35-55-specific T cell line was also enhanced by NK cell deletion in B6, beta 2m-/-, and recombination activation gene 2 (RAG-2)-/- mice, indicating that the regulation by NK cells can be independent of T, B, or NK-T cells. We further showed that NK cells inhibit T cell proliferation triggered by antigen or cytokine stimulation. Taken together, we conclude that NK cells are an important regulator for EAE in both induction and effector phases.

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Effect of anti-NK1.1 mAb on MOG35-55 induced EAE in IFN-γ−/− mice. The mice were immunized two times with MOG35-55 peptide for  EAE induction. 1 d before first immunization, the mice were intravenously injected with control mAb (A) or anti-NK1.1 mAb (B). The result of pretreatment with PBS did not differ from results shown in A or B.
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Figure 4: Effect of anti-NK1.1 mAb on MOG35-55 induced EAE in IFN-γ−/− mice. The mice were immunized two times with MOG35-55 peptide for EAE induction. 1 d before first immunization, the mice were intravenously injected with control mAb (A) or anti-NK1.1 mAb (B). The result of pretreatment with PBS did not differ from results shown in A or B.

Mentions: NK cell activity is known to be impaired in IFN-γ−/− mice (29). This information prompts us to study the effect of NK cell deletion on EAE in this mutant strain. Interestingly, the spleen in the mutant was only one-fourth the size of that of wild-type mice. In addition, the proportion of NK cells (NK1.1+CD3− cells) in the total spleen cells was markedly reduced (1.0% in IFN-γ−/− versus 5.0% in wild-type), indicating that the development of NK cells is impaired in the mutant due to the genetic defect. As shown in Fig. 4, IFN-γ−/− mice immunized with MOG35-55 developed monophasic EAE which is more serious and uniform than wild-type B6 mice. Notably, pretreatment with anti-NK1.1 mAb showed no obvious effects on the clinical course (Fig. 4, Table 1). These results allowed us to interpret that the regulation mediated by NK cells is reduced in IFN-γ−/− mice, probably due to the decreased number as well as impaired regulatory function of NK cells. It remains unclear how the gene defect leads to the NK cell dysfunction.


Regulation of experimental autoimmune encephalomyelitis by natural killer (NK) cells.

Zhang B, Yamamura T, Kondo T, Fujiwara M, Tabira T - J. Exp. Med. (1997)

Effect of anti-NK1.1 mAb on MOG35-55 induced EAE in IFN-γ−/− mice. The mice were immunized two times with MOG35-55 peptide for  EAE induction. 1 d before first immunization, the mice were intravenously injected with control mAb (A) or anti-NK1.1 mAb (B). The result of pretreatment with PBS did not differ from results shown in A or B.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199138&req=5

Figure 4: Effect of anti-NK1.1 mAb on MOG35-55 induced EAE in IFN-γ−/− mice. The mice were immunized two times with MOG35-55 peptide for EAE induction. 1 d before first immunization, the mice were intravenously injected with control mAb (A) or anti-NK1.1 mAb (B). The result of pretreatment with PBS did not differ from results shown in A or B.
Mentions: NK cell activity is known to be impaired in IFN-γ−/− mice (29). This information prompts us to study the effect of NK cell deletion on EAE in this mutant strain. Interestingly, the spleen in the mutant was only one-fourth the size of that of wild-type mice. In addition, the proportion of NK cells (NK1.1+CD3− cells) in the total spleen cells was markedly reduced (1.0% in IFN-γ−/− versus 5.0% in wild-type), indicating that the development of NK cells is impaired in the mutant due to the genetic defect. As shown in Fig. 4, IFN-γ−/− mice immunized with MOG35-55 developed monophasic EAE which is more serious and uniform than wild-type B6 mice. Notably, pretreatment with anti-NK1.1 mAb showed no obvious effects on the clinical course (Fig. 4, Table 1). These results allowed us to interpret that the regulation mediated by NK cells is reduced in IFN-γ−/− mice, probably due to the decreased number as well as impaired regulatory function of NK cells. It remains unclear how the gene defect leads to the NK cell dysfunction.

Bottom Line: The disease enhancement was associated with augmentation of T cell proliferation and production of Th1 cytokines in response to MOG35-55.We further showed that NK cells inhibit T cell proliferation triggered by antigen or cytokine stimulation.Taken together, we conclude that NK cells are an important regulator for EAE in both induction and effector phases.

View Article: PubMed Central - PubMed

Affiliation: Department of Demyelinating Disease and Aging, National Institute of Neuroscience, Tokyo, Japan.

ABSTRACT
In this report, we establish a regulatory role of natural killer (NK) cells in experimental autoimmune encephalomyelitis (EAE), a prototype T helper cell type 1 (Th1)-mediated disease. Active sensitization of C57BL/6 (B6) mice with the myelin oligodendrocyte glycoprotein (MOG)35-55 peptide induces a mild form of monophasic EAE. When mice were deprived of NK cells by antibody treatment before immunization, they developed a more serious form of EAE associated with relapse. Aggravation of EAE by NK cell deletion was also seen in beta 2-microglobulin-/- (beta 2m-/-) mice, indicating that NK cells can play a regulatory role in a manner independent of CD8+ T cells or NK1.1+ T cells (NK-T cells). The disease enhancement was associated with augmentation of T cell proliferation and production of Th1 cytokines in response to MOG35-55. EAE passively induced by the MOG35-55-specific T cell line was also enhanced by NK cell deletion in B6, beta 2m-/-, and recombination activation gene 2 (RAG-2)-/- mice, indicating that the regulation by NK cells can be independent of T, B, or NK-T cells. We further showed that NK cells inhibit T cell proliferation triggered by antigen or cytokine stimulation. Taken together, we conclude that NK cells are an important regulator for EAE in both induction and effector phases.

Show MeSH
Related in: MedlinePlus