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Antiviral CD8+ T cells cause an experimental autoimmune encephalomyelitis-like disease in naive mice

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Abstract

Major histocompatibility complex class I-restricted CD8+ cytotoxic T lymphocytes are involved in the pathogenesis of multiple sclerosis (MS) and both autoimmune, experimental autoimmune encephalomyelitis, and viral, Theiler’s murine encephalomyelitis virus (TMEV) infection, animal models of MS. Following TMEV infection, certain T cell hybridomas, generated from cloned TMEV-induced CD8+ T cells, were able to produce clinical signs of disease (flaccid hind limb paralysis) upon adoptive transfer into naive mice. Dual T cell receptors (TCR) are present on the surface of these cells as both Vβ3 and Vβ6 were detected by polymerase chain reaction (PCR) screening and flow cytometry and multiple Vα mRNAs were detected by PCR screening. This is the first demonstration of antiviral CD8+ T cells having more than one TCR initiating an autoimmune disease in the natural host of the virus. We hypothesize that this is a potential mechanism for virus-induced autoimmune disease initiated by CD8+ T cells.

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Acknowledgment

We wish to thank Nikki J. Kennett, BS, Daniel J. Doty, and Braden T. McElreath for excellent technical assistance. We wish to acknowledge Kathleen Borick for the outstanding preparation of the manuscript. This work was supported by funding from NIH [5R01NS34497 (R.S.), R21NS059724 (I.T.), P20-RR018724 (I.T.)], and the Emma Mary Deland Foundation (R.S.).

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Authors and Affiliations

  1. Department of Pathology, University of Utah School of Medicine, 30 North 1900 East, 3R330 SOM, Salt Lake City, UT, 84132, USA

    Jane E. Libbey, Matthew F. Cusick & Robert S. Fujinami

  2. Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA, 71130, USA

    Ikuo Tsunoda

  3. Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA, 71130, USA

    Ikuo Tsunoda

Authors
  1. Jane E. Libbey
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  2. Matthew F. Cusick
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  3. Ikuo Tsunoda
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  4. Robert S. Fujinami
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Correspondence to Robert S. Fujinami.

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Libbey, J.E., Cusick, M.F., Tsunoda, I. et al. Antiviral CD8+ T cells cause an experimental autoimmune encephalomyelitis-like disease in naive mice. J. Neurovirol. 18, 45–54 (2012). https://doi.org/10.1007/s13365-012-0077-2

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