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Susceptibility to Theiler’s murine encephalomyelitis virus-induced demyelinating disease in BALB/cAnNCr mice is related to absence of a CD4+ T-cell subset

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

P W Denton

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

R W Melvold

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, rmelvold{at}medicine.nodak.edu

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-IDD) - 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.

Key Words: demyelination • immune regulation • multiple sclerosis • Theiler's virus

Multiple Sclerosis, Vol. 8, No. 6, 469-474 (2002)
DOI: 10.1191/1352458502ms850oa


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