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The effects of restraint stress (RS) on immune responses to Theiler’s murine encephalomyelitis virus (TMEV) in SJL mice
Author(s) -
Steelman Andrew,
Prentice Thomas,
Young Colin,
Dean Dana,
Hammons Ashley,
Meagher Mary,
Welsh Jane
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1393-b
Subject(s) - immune system , immunology , cd8 , biology , splenocyte , virus , viral load , antigen , t cell , virology
We have investigated the effects of stress on the pathogenesis of TMEV– an animal model for human MS, in which viral persistence results in autoimmune‐mediated demyelination. We examined the effects of RS on behavioral and immune responses to TMEV. RS altered body weight, temperatures and activity levels. We found that RS reduced virus specific immunodominant CD4 and CD8 T cell responses in the spleens of infected animals, using ELISPOT assays. Additionally, the virus specific immunodominant CD8 response was reduced in the central nervous system of infected animals. RS significantly decreased both Type 1 {IL‐12(p40), IL‐12(p70), IFN‐g} and Type 2 (IL‐4 and IL‐5) serum protein concentrations as measured by Bioplex. Splenic mRNA expression levels of the transcription factors T‐bet and GATA‐3 – the drivers of Th1 and Th2 polarization respectively, were decreased. RS also caused decreased serum concentrations of RANTES and MCP‐1, but increased IL‐6, KC, and G‐CSF protein concentrations. These data indicate that RS results in a general suppression of immune responses to TMEV that may stem from a direct effect on antigen presenting cells. In conclusion, decreased immune responses (CD4 and CD8), in early TMEV infection can account for both the increased viral titers, increased viral persistence, and earlier onset of more severe demyelinating disease in stressed mice. Funded by NIH/NINDS R01 39569 C.J.R.W. & M.W.M.