Susceptibility to Theiler's murine encephalomyelitis virus-induced demyelinating disease in BALB/cAnNCr mice is related to absence of a CD4+ T-cell subset.
Two histocompatible substrains of BALB/c mice (BALB/cByJ, BALB/cAnNCr) are resistant and susceptible, respectively, to Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-1DD)--a model for viral etiology of human multiple sclerosis. BALB/cByJ mice become susceptible following low-dose irradiation given prior to infection. Resistance is restored by adoptive transfer of CD8+ (but not CD4+) splenic T cells from infected, unirradiated BALB/cByJ donors. In contrast resistance is conferred to BALB/cAnNCr mice by adoptive transfer of either CD4+ or CD8+ T cells from resistant BALB/cByJ donors. T cells from BALB/cAnNCr mice cannot confer protection. To integrate these two observations, we hypothesized that the BALB/cAnNCr mice possess precursors of the regulatory CD8+ T cells, but fail to activate them because they lack a critical CD4+ T-cell subpopulation. We tested this model using serial transfers. The transfer of CD4+ T cells from the BALB/cByJ to the BALB/cAnNCr mice permitted development of BALB/cAnNCr CD8+ T cells that in turn, provided resistance when transferred into susceptible recipients. The BALB/cByJ CD4+ T cells, which activated the CD8+ cells, were sensitive to low-dose irradiation, unlike CD4+ T cells involved in the later inflammatory demyelination. Thus, susceptibility of BALB/cAnNCr mice is due to a defective/absent CD4+ T-cell subset acting immediately after infection.
Karls
K A
KA
Department of Microbiology and Immunology, School of Medicine and Health Sciences, University of North Dakota, 501 North Columbia Road, Grand Forks, North Dakota 58202, USA.
Denton
P W
PW
Melvold
R W
RW
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000528:radiation effects; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018188:Cardiovirus Infections / Q000276:immunology*; D003711:Demyelinating Diseases / Q000276:immunology* / Q000821:virology*; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D017945:Theilovirus