The Th1/Th2 balance does not account for the difference of susceptibility of mouse strains to Theiler's virus persistent infection

Theiler's virus causes a persistent infection with demyelination that is st udied as a model for multiple sclerosis, Inbred strains of mice differ in t heir susceptibility to viral persistence due to both H-2 and non-H-2 genes. A locus with a major effect on persistence has been mapped on chromosome 1 0, dose to the Ifng locus, using a cross between susceptible SJL/J and resi stant B10.S mice. We now confirm the existence of this locus using two line s of congenic mice bearing the B10.S Ifng locus on an SJL/J background, and we describe a deletion in the promoter of the Ifng gene of the SJL/J mouse . We studied the expression of IFN-gamma, IL-2, IL-10, and IL-12 in the bra ins of SJL/J mice, B10.S mice, and the two lines of congenic mice during th e first 2 wk following inoculation. We found a greater expression of IFN-ga mma and IL-2 mRNA in the brains of B10.S mice compared with those of SJL/J mice. Also, the ratio of IL-12 to IL-10 mRNA levels was higher in B10.S mic e. However,the :cytokine profiles were the same for the two lines of resist ant congenic mice and for susceptible SJL/J mice. Therefore, the difference of Th1/Th2 balance between the B10.S and SJL/J mice is not due to the Ifng locus and does not account for the, difference of susceptibility of these mice to persistent infection.