Multiple Sclerosis, 1 October 2002, vol. 8, no. 6, pp. 469-474(6)
Karls K.A.; Denton P.W.; Melvold R.W.
 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
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.