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Natural killer cells determine the outcome of B cell–mediated autoimmunity

Nature Immunology volume 1, pages 245–251 (2000)Cite this article

Abstract

Natural killer (NK) cells can affect the outcome of adaptive immune responses. NK cells, but not NK1.1+ T cells, were found to participate in the development of myasthenia gravis (a T cell–dependent, B cell– and antibody-mediated autoimmune disease) in C57BL/6 mice. The requirement for NK cells was reflected by the lack of a type 1 helper T cell response and antibodies to the acetylcholine receptor in both NK1.1+ cell–depleted and NK cell–deficient IL-18−/− mice. These findings establish a previously unrecognized link between NK cells and autoreactive T and B cells.

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Figure 1: Incidence and severity of EAMG in NK1.1+ cell–depleted and NKT cell–deficient mice.
Figure 2: Functional properties of NK cells in EAMG.
Figure 3: NK1.1+ cell depletion before immunization with AChR + CFA leads to enhanced TGF-β1 production by T cells that down-regulate TH1 type immune responses.
Figure 4: NK1.1+ cell depletion before immunization with AChR and CFA impairs anti-AChR IgG and IgG2b isotype responses.
Figure 5: Effects of NKT cell deficiency on autoreactive T and B cell responses.
Figure 6: Resistance to EAMG induction in IL-18−/− mice is associated with defective NK cell function.

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Acknowledgements

We thank N. Sarvetnick for reading the manuscript; T. Takeda and S. Akira for IL-18 mutant mice; M. T. Bejarano, L. Cervenak and members of the Ljunggren group for discussions; P. H. van der Meide, B. Wahren, M. Levi, M. Mustafa and M. Korsgren for antibodies and other reagents; M. L. Solberg, M. Hagelin and B. Wester for technical assistance. Supported by grants from the Swedish Medical Research Council, the Swedish Multiple Sclerosis Society, the Swedish Cancer Society, the Petrus and Augusta Hedlund foundation, the Lars Hierta foundation, the Magnus Bergwall foundation, the Åke Wiberg foundation and the Karolinska Institutet.

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Author notes

  1. Fu-Dong Shi

    Present address: Department of Immunology, IMM-23, The Scripps Research Institute, 10555 North Torrey Pines Road, La Jolla, CA, 92037, USA

  2. Fu-Dong Shi, Hua-Bing Wang and Hulun Li: These authors contributed equally to this work.

Authors and Affiliations

  1. Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, S-171 77, Sweden

    Fu-Dong Shi & Hans-Gustaf Ljunggren

  2. Division of Neurology, Huddinge University Hospital, Karolinska Institutet, Stockholm, S-141 86, Sweden

    Hua-Bing Wang, Hulun Li & Hans Link

  3. Department of Microbiology and Immunology, Howard Hughes Medical Institute, Vanderbilt University School of Medicine, Nashville, 37232, TN, USA

    Seokmann Hong & Luc Van Kaer

  4. Division of Molecular Immunology, Center for Biomedical Science, School of Medicine, Chiba University, 1-8-1 Inobana, Chuo-ku, Chiba, 260, Japan

    Masaru Taniguchi

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Correspondence to Hans-Gustaf Ljunggren.

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Shi, FD., Wang, HB., Li, H. et al. Natural killer cells determine the outcome of B cell–mediated autoimmunity. Nat Immunol 1, 245–251 (2000). https://doi.org/10.1038/79792

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