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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 wild-type B6 mice. Mice were immunized two times with the MOG35-55 for EAE  induction. They were intravenously injected with PBS, 500 μg of control mAb (M-11; A), or 500 μg of anti-NK1.1 mAb (PK136; B) 1 d before first immunization with the MOG peptide. Clinical score of individual mice at each observation time point is shown by different marks. This is a representative  of two experiments with similar results. The result of pretreatment with PBS did not differ significantly from that with control mAb.
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Figure 1: Effect of anti-NK1.1 mAb on MOG35-55 induced EAE in wild-type B6 mice. Mice were immunized two times with the MOG35-55 for EAE induction. They were intravenously injected with PBS, 500 μg of control mAb (M-11; A), or 500 μg of anti-NK1.1 mAb (PK136; B) 1 d before first immunization with the MOG peptide. Clinical score of individual mice at each observation time point is shown by different marks. This is a representative of two experiments with similar results. The result of pretreatment with PBS did not differ significantly from that with control mAb.

Mentions: Immunization with MOG35-55 induced a mild form of monophasic EAE with transient loss of tail tone in untreated B6 mice and the mice injected with PBS or control mAb (Fig. 1 A, Table 1). Although the original report (26) described the induction of chronic, nonremitting EAE by this protocol, we have not seen such a serious form of EAE in any of the mice. The difference could be due to variances in mouse substrains or reagents used for immunization. To know the functional role of NK cells, EAE was induced in mice deprived of NK cells with anti-NK1.1 mAb. Control mice were pretreated with isotype-matched control mAb (M-11). Preparatory experiments revealed that the injection of anti-NK1.1 mAb completely deleted NK1.1+ population from the peripheral blood and the spleen within 24 h after antibody injection, which lasted for as long as 5 wk, whereas control mAb induced only a mild, transient loss of NK1.1+ cells (Fig. 2). This was consistent with the description that the mAb is effective in depleting NK cells in vivo (13, 15–17). In addition, we confirmed that mAbs reactive to the allotype of the anti-NK1.1 mAb (anti-IgG2a) did not stain spleen cells of the mice on 24 h, 72 h, 7 d, and 16 d after injection of anti-NK1.1. This excludes the possibility that antibody-coated NK1.1+ cells may remain but cannot be detected due to blocking of NK1.1 epitope.


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 wild-type B6 mice. Mice were immunized two times with the MOG35-55 for EAE  induction. They were intravenously injected with PBS, 500 μg of control mAb (M-11; A), or 500 μg of anti-NK1.1 mAb (PK136; B) 1 d before first immunization with the MOG peptide. Clinical score of individual mice at each observation time point is shown by different marks. This is a representative  of two experiments with similar results. The result of pretreatment with PBS did not differ significantly from that with control mAb.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Effect of anti-NK1.1 mAb on MOG35-55 induced EAE in wild-type B6 mice. Mice were immunized two times with the MOG35-55 for EAE induction. They were intravenously injected with PBS, 500 μg of control mAb (M-11; A), or 500 μg of anti-NK1.1 mAb (PK136; B) 1 d before first immunization with the MOG peptide. Clinical score of individual mice at each observation time point is shown by different marks. This is a representative of two experiments with similar results. The result of pretreatment with PBS did not differ significantly from that with control mAb.
Mentions: Immunization with MOG35-55 induced a mild form of monophasic EAE with transient loss of tail tone in untreated B6 mice and the mice injected with PBS or control mAb (Fig. 1 A, Table 1). Although the original report (26) described the induction of chronic, nonremitting EAE by this protocol, we have not seen such a serious form of EAE in any of the mice. The difference could be due to variances in mouse substrains or reagents used for immunization. To know the functional role of NK cells, EAE was induced in mice deprived of NK cells with anti-NK1.1 mAb. Control mice were pretreated with isotype-matched control mAb (M-11). Preparatory experiments revealed that the injection of anti-NK1.1 mAb completely deleted NK1.1+ population from the peripheral blood and the spleen within 24 h after antibody injection, which lasted for as long as 5 wk, whereas control mAb induced only a mild, transient loss of NK1.1+ cells (Fig. 2). This was consistent with the description that the mAb is effective in depleting NK cells in vivo (13, 15–17). In addition, we confirmed that mAbs reactive to the allotype of the anti-NK1.1 mAb (anti-IgG2a) did not stain spleen cells of the mice on 24 h, 72 h, 7 d, and 16 d after injection of anti-NK1.1. This excludes the possibility that antibody-coated NK1.1+ cells may remain but cannot be detected due to blocking of NK1.1 epitope.

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