CD8(+) T cells from Theiler's virus-resistant BALB/cByJ mice downregulate pathogenic virus-specific CD4(+) T cells.
Theiler's murine encephalomyelitis virus (TMEV) is a picornavirus which induces an immune-mediated demyelinating disease in susceptible strains of mice and serves as a relevant animal model for multiple sclerosis. Treatment with low dose irradiation prior to infection with the BeAn strain of TMEV renders the genetically resistant BALB/cByJ (C/cByJ) mice susceptible to disease. Previous studies have shown that disease resistance in the C/cByJ is mediated by a 'regulatory' CD8(+) T cell population, which does not appear to function via a cytolytic mechanism. We show here that TMEV-specific CD4(+) T cell blasts transferred into susceptible, irradiated C/cByJ accelerate clinical disease and enhance TMEV-specific DTH and proliferation in these animals. Significantly, CD8(+) cells from infected, resistant C/cByJ mice specifically downregulate the in vivo disease potentiation and diminish virus specific DTH, and proliferative and pro-inflammatory cytokine responses (IFNgamma and IL-2) in recipients of TMEV-specific CD4(+) T cell blasts. These results indicate that TMEV infection of resistant C/cByJ mice induces a radiosensitive population of regulatory CD8(+) T cells which actively downregulate inherent Th1 responses which have disease initiating potential.
Haynes
L M
LM
Department of Microbiology-Immunology, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611, USA.
Vanderlugt
C L
CL
Dal Canto
M C
MC
Melvold
R W
RW
Miller
S D
SD
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D018188:Cardiovirus Infections / Q000209:etiology*; D002455:Cell Division / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D003711:Demyelinating Diseases / Q000276:immunology* / Q000821:virology*; D004198:Disease Susceptibility; D015536:Down-Regulation; D006968:Hypersensitivity, Delayed / Q000503:physiopathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D018417:Th1 Cells / Q000378:metabolism; D017945:Theilovirus / Q000276:immunology*
D016207:Cytokines