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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 passive EAE in RAG-2βˆ’/βˆ’ mice and the treatment with spleen cells. 5 Γ— 105 of activated ZB-1 line cells were  intravenously transferred into (A) RAG-2βˆ’/βˆ’ mice pretreated on day βˆ’1 with control mAb (A) or with anti-NK1.1 mAb (B, C, and D). The mice were  injected with 500 ng PT after cell transfer. Although mice in B did not receive any further manipulation, 2 Γ— 107 of spleen cells from RAG-2βˆ’/βˆ’ mice  were intravenously transferred to mice in C on day 2 and the same number of spleen cells from RAG-2βˆ’/βˆ’ mice which had been pretreated with anti-NK1.1 mAb on day βˆ’1, were intravenously transferred to mice in D. This is a representative of two experiments with similar results.
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Figure 8: Effect of NK cell deletion on passive EAE in RAG-2βˆ’/βˆ’ mice and the treatment with spleen cells. 5 Γ— 105 of activated ZB-1 line cells were intravenously transferred into (A) RAG-2βˆ’/βˆ’ mice pretreated on day βˆ’1 with control mAb (A) or with anti-NK1.1 mAb (B, C, and D). The mice were injected with 500 ng PT after cell transfer. Although mice in B did not receive any further manipulation, 2 Γ— 107 of spleen cells from RAG-2βˆ’/βˆ’ mice were intravenously transferred to mice in C on day 2 and the same number of spleen cells from RAG-2βˆ’/βˆ’ mice which had been pretreated with anti-NK1.1 mAb on day βˆ’1, were intravenously transferred to mice in D. This is a representative of two experiments with similar results.

Mentions: Next we injected the line cells into RAG-2βˆ’/βˆ’ mice, which lack T, B, and NK–T cells due to the defect in the recombination machinery. Transfer of 107 or 3 Γ— 106 cells induced a hyperacute, lethal form of EAE in untreated RAG-2βˆ’/βˆ’ mice (data not shown). This indicates that the RAG-2βˆ’/βˆ’ mice are more prone to passive EAE than wild-type or Ξ²2mβˆ’/βˆ’ mice, probably due to the absence of regulatory cells bearing clonotypic receptors. In contrast, when the number of transferred cells was reduced to 5 Γ— 105, EAE was not induced in control RAG-2βˆ’/βˆ’ mice. However, if NK cells were deleted in vivo, the same number of cells induced hyperacute EAE within 5–6 d after cell transfer (Fig. 8 B). Notably, this lethal disease was completely prevented by transfer of 2 Γ— 107 spleen cells of normal RAG-2βˆ’/βˆ’ mice, which contain 4 Γ— 106 NK cells (Fig. 8 C). In contrast, the same number of spleen cells of RAG-2βˆ’/βˆ’ mice deprived of NK cells with anti-NK1.1 mAb showed no ameliorating effects (Fig. 8 D). These results indicate that NK cells of RAG-2βˆ’/βˆ’ mice play a regulatory role, whereas non–NK cells from the mutant strain do not.


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 passive EAE in RAG-2βˆ’/βˆ’ mice and the treatment with spleen cells. 5 Γ— 105 of activated ZB-1 line cells were  intravenously transferred into (A) RAG-2βˆ’/βˆ’ mice pretreated on day βˆ’1 with control mAb (A) or with anti-NK1.1 mAb (B, C, and D). The mice were  injected with 500 ng PT after cell transfer. Although mice in B did not receive any further manipulation, 2 Γ— 107 of spleen cells from RAG-2βˆ’/βˆ’ mice  were intravenously transferred to mice in C on day 2 and the same number of spleen cells from RAG-2βˆ’/βˆ’ mice which had been pretreated with anti-NK1.1 mAb on day βˆ’1, were intravenously transferred to mice in D. This is a representative of two experiments with similar results.
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Related In: Results  -  Collection

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Figure 8: Effect of NK cell deletion on passive EAE in RAG-2βˆ’/βˆ’ mice and the treatment with spleen cells. 5 Γ— 105 of activated ZB-1 line cells were intravenously transferred into (A) RAG-2βˆ’/βˆ’ mice pretreated on day βˆ’1 with control mAb (A) or with anti-NK1.1 mAb (B, C, and D). The mice were injected with 500 ng PT after cell transfer. Although mice in B did not receive any further manipulation, 2 Γ— 107 of spleen cells from RAG-2βˆ’/βˆ’ mice were intravenously transferred to mice in C on day 2 and the same number of spleen cells from RAG-2βˆ’/βˆ’ mice which had been pretreated with anti-NK1.1 mAb on day βˆ’1, were intravenously transferred to mice in D. This is a representative of two experiments with similar results.
Mentions: Next we injected the line cells into RAG-2βˆ’/βˆ’ mice, which lack T, B, and NK–T cells due to the defect in the recombination machinery. Transfer of 107 or 3 Γ— 106 cells induced a hyperacute, lethal form of EAE in untreated RAG-2βˆ’/βˆ’ mice (data not shown). This indicates that the RAG-2βˆ’/βˆ’ mice are more prone to passive EAE than wild-type or Ξ²2mβˆ’/βˆ’ mice, probably due to the absence of regulatory cells bearing clonotypic receptors. In contrast, when the number of transferred cells was reduced to 5 Γ— 105, EAE was not induced in control RAG-2βˆ’/βˆ’ mice. However, if NK cells were deleted in vivo, the same number of cells induced hyperacute EAE within 5–6 d after cell transfer (Fig. 8 B). Notably, this lethal disease was completely prevented by transfer of 2 Γ— 107 spleen cells of normal RAG-2βˆ’/βˆ’ mice, which contain 4 Γ— 106 NK cells (Fig. 8 C). In contrast, the same number of spleen cells of RAG-2βˆ’/βˆ’ mice deprived of NK cells with anti-NK1.1 mAb showed no ameliorating effects (Fig. 8 D). These results indicate that NK cells of RAG-2βˆ’/βˆ’ mice play a regulatory role, whereas non–NK cells from the mutant strain do not.

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