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Anti-MS4a4B treatment abrogates MS4a4B-mediated protection in T cells and ameliorates experimental autoimmune encephalomyelitis

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Abstract

Recent data show that anti-CD20 therapy is effective for some autoimmune diseases, including multiple sclerosis (MS). However, the efficacy of anti-CD20 therapy for MS is largely limited because anti-CD20 antibodies target only B cells. In previous studies, we have investigated the function of MS4a4B, a novel CD20 homologue, in T cell proliferation. Here, we found that MS4a4B regulates not only T cell proliferation but also T cell apoptosis. Knockdown of MS4a4B by MS4a4B-siRNA or MS4a4B-shRNA-expressing vector promoted apoptosis in primary T cells and T32 cell line. In contrast, vector-driven over-expression of MS4a4B reduced apoptosis in EL-4 cells. Machinery analysis showed that MS4a4B-mediated T cell survival was associated with decreased activity of caspases 3, 8 and 9. Interestingly, binding of anti-MS4a4B antibodies to T cells induced activated T cells to undergo apoptosis. To test whether anti-MS4a4B antibody interferes with MS4a4B-mediated protection of T cells, we injected anti-MS4a4B antibodies into mice with experimental autoimmune encephalomyelitis (EAE). The results show that anti-MS4a4B treatment ameliorated the severity of EAE, accompanied by decreased Th1 and Th17 cell responses and reduced levels of pro-inflammatory cytokines in the central nervous system, suggesting that MS4a4B may serve as a target of antibody-based therapy for T cell-mediated diseases.

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Acknowledgments

We are grateful to Katherine Regan for editorial assistance. We thank Hong Dai and Ke Li for helpful technical assistance. This work was supported by Grants from the American Heart Association (H.X.) and from the National Institutes of Health (A.M.R.).

Conflict of interest

The authors declare that they have no competing financial interests.

Author information

Authors and Affiliations

  1. Department of Neurology, Thomas Jefferson University, 900 Walnut Street, JHN 300, Philadelphia, PA, 19107, USA

    Yaping Yan, Zichen Li, Guang-Xian Zhang, Abdolmohamad Rostami & Hui Xu

  2. Department of Microbiology and Immunology, University of Maryland School of Medicine, 800 W Baltimore Street, Baltimore, MD, 21201, USA

    Mark S. Williams & Gregory B. Carey

  3. Department of Microbiology and Immunology, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA, 19107, USA

    Jianke Zhang

  4. Division of Therapeutic Proteins, Center for Drug Evaluation and Research, Food and Drug Administration, 29 Lincoln Drive, Bethesda, MD, 20892, USA

    Hui Xu

Authors
  1. Yaping Yan
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  2. Zichen Li
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  3. Guang-Xian Zhang
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  7. Abdolmohamad Rostami
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Corresponding authors

Correspondence to Abdolmohamad Rostami or Hui Xu.

Additional information

Yaping Yan and Zichen Li have contributed equally to this study.

H. Xu is the primary corresponding author.

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Yan, Y., Li, Z., Zhang, GX. et al. Anti-MS4a4B treatment abrogates MS4a4B-mediated protection in T cells and ameliorates experimental autoimmune encephalomyelitis. Apoptosis 18, 1106–1119 (2013). https://doi.org/10.1007/s10495-013-0870-2

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  • DOI: https://doi.org/10.1007/s10495-013-0870-2

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