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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 45-54 |
| Number of pages | 10 |
| Journal | Journal of neurovirology |
| Volume | 18 |
| Issue number | 1 |
| DOIs | |
| State | Published - Feb 2012 |
Funding
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.).
Keywords
- Adoptive transfer
- Autoimmune
- CD8 cytotoxic T lymphocytes
- Dual T cell receptor
- Hybridomas
- Multiple sclerosis
- Theiler's murine encephalomyelitis virus
ASJC Scopus subject areas
- Neurology
- Clinical Neurology
- Cellular and Molecular Neuroscience
- Virology
