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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 NK cell deletion on antigen-induced proliferation of T line cells. ZB-1 T line cells (4 × 104 cells/well) were stimulated with  MOG35-55 in the presence of x irradiated spleen cells (8 × 105 cells/well) from wild-type B6 (A) or β2m−/− mice (B). In each experiment, spleen cells  from mice pretreated with control mAb (control) and those pretreated with anti-NK1.1 mAb (anti-NK1.1) were compared in their accessory function.  Data represent mean cpm ± SD of triplicate cultures. This is a representative of three experiments with similar results.
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Figure 9: Effect of NK cell deletion on antigen-induced proliferation of T line cells. ZB-1 T line cells (4 × 104 cells/well) were stimulated with MOG35-55 in the presence of x irradiated spleen cells (8 × 105 cells/well) from wild-type B6 (A) or β2m−/− mice (B). In each experiment, spleen cells from mice pretreated with control mAb (control) and those pretreated with anti-NK1.1 mAb (anti-NK1.1) were compared in their accessory function. Data represent mean cpm ± SD of triplicate cultures. This is a representative of three experiments with similar results.

Mentions: To obtain insights into the mechanism of NK cell–mediated regulation, we conducted in vitro experiments, assaying antigen-induced proliferation of ZB-1 cells in the presence of irradiated spleen cells as APCs. First, spleen cells from NK cell–deleted mice were compared with those from control mice as accessory cells for ZB-1 line cells. The experiment showed that antigen-induced ZB-1 cell proliferation is enhanced when spleen cells were derived from NK-deleted mice. We obtained similar results not only with spleen cells from wild-type B6 mice, but also from β2m−/− mice (Fig. 9, A and B). These indicate that irradiated, spleen NK cells would inhibit antigen-induced Th1 proliferation. Notably, the proliferative responses obtained by using different sources of spleen APCs roughly correlated with clinical grade of EAE and Th1 cytokine levels in the sera (Table 2), supporting the relevance of the in vitro system for estimating in vivo conditions.


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 NK cell deletion on antigen-induced proliferation of T line cells. ZB-1 T line cells (4 × 104 cells/well) were stimulated with  MOG35-55 in the presence of x irradiated spleen cells (8 × 105 cells/well) from wild-type B6 (A) or β2m−/− mice (B). In each experiment, spleen cells  from mice pretreated with control mAb (control) and those pretreated with anti-NK1.1 mAb (anti-NK1.1) were compared in their accessory function.  Data represent mean cpm ± SD of triplicate cultures. This is a representative of three experiments with similar results.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 9: Effect of NK cell deletion on antigen-induced proliferation of T line cells. ZB-1 T line cells (4 × 104 cells/well) were stimulated with MOG35-55 in the presence of x irradiated spleen cells (8 × 105 cells/well) from wild-type B6 (A) or β2m−/− mice (B). In each experiment, spleen cells from mice pretreated with control mAb (control) and those pretreated with anti-NK1.1 mAb (anti-NK1.1) were compared in their accessory function. Data represent mean cpm ± SD of triplicate cultures. This is a representative of three experiments with similar results.
Mentions: To obtain insights into the mechanism of NK cell–mediated regulation, we conducted in vitro experiments, assaying antigen-induced proliferation of ZB-1 cells in the presence of irradiated spleen cells as APCs. First, spleen cells from NK cell–deleted mice were compared with those from control mice as accessory cells for ZB-1 line cells. The experiment showed that antigen-induced ZB-1 cell proliferation is enhanced when spleen cells were derived from NK-deleted mice. We obtained similar results not only with spleen cells from wild-type B6 mice, but also from β2m−/− mice (Fig. 9, A and B). These indicate that irradiated, spleen NK cells would inhibit antigen-induced Th1 proliferation. Notably, the proliferative responses obtained by using different sources of spleen APCs roughly correlated with clinical grade of EAE and Th1 cytokine levels in the sera (Table 2), supporting the relevance of the in vitro system for estimating in vivo conditions.

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