Restraint stress modulates virus specific adaptive immunity during acute Theiler's virus infection.
Multiple sclerosis (MS) is a devastating CNS disease of unknown origin. Multiple factors including genetic background, infection, and psychological stress affect the onset or progression of MS. Theiler's murine encephalomyelitis virus (TMEV) infection is an animal model of MS in which aberrant immunity leads to viral persistence and subsequently results in demyelination that resembles MS. Here, we examined how stress during acute TMEV infection altered virus-specific cell mediated responses. Using immunodominant viral peptides specific for either CD4(+) or CD8(+) T cells, we found that stress reduced IFN-gamma producing virus-specific CD4(+) and CD8(+) T cells in the spleen and CD8(+) T cells CNS. Cytokine production by cells isolated from the CNS or spleens following stimulation with virus or viral peptides, indicated that stress decreased both type 1 and type 2 responses. Glucocorticoids were implicated in the decreased T cell function as the effects of stress were partially reversed by concurrent RU486 administration but mimicked by dexamethasone. As T cells mediate viral clearance in this model, our data support the hypothesis that stress-induced immunosuppression may provide a mechanism for enhanced viral persistence within the CNS.
Department of Veterinary Integrative Biosciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843-4458, USA.
Andrew J
AJ
Steelman
Dana D
DD
Dean
Colin R
CR
Young
Roger
R
Smith
Thomas W
TW
Prentice
Mary W
MW
Meagher
C Jane R
CJ
Welsh
D000208:Acute Disease; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018188:Cardiovirus Infections / Q000276:immunology* / Q000523:psychology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D050990:GATA3 Transcription Factor / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology / Q000502:physiology; D007111:Immunity, Cellular / Q000502:physiology*; D051379:Mice; D012149:Restraint, Physical; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013315:Stress, Psychological / Q000276:immunology* / Q000523:psychology*; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology; D017945:Theilovirus / Q000276:immunology* / Q000302:isolation & purification; D010948:Viral Plaque Assay
D016207:Cytokines; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse