The importance of antibody and CD8+ cells in resolution of murine rotavirus (EDIM) infection and protection against reinfection was examined with two strains of B-cell-deficient mice. Following inoculation of one strain (JHD), rotavirus infection was resolved within days, but when later reinoculated with EDIM, these mice again shed rotavirus. Thus, effector mechanisms other than antibody resolved viral shedding in JHD mice but were insufficient to prevent reinfection. EDIM shedding in another B-cell-deficient mouse strain (microMT) diminished but was not fully resolved 93 days after the initial infection, thus demonstrating that antibody could also be important in resolution of rotavirus infection. When depleted of CD8+ cells by monoclonal antibody treatment before EDIM inoculation, JHD mice were unable to resolve shedding. Even though microMT mice did not fully resolve their initial infection, depletion of CD8+ cells 49 days after initial inoculation resulted in a burst of shedding. Thus, CD8+ cells were involved in resolution of the initial EDIM infection in both strains of B-cell-deficient mice. Finally, when microMT mice were depleted of CD8+ cells before the initial EDIM infection, gradual resolution of rotavirus shedding was still observed, suggesting a third effector mechanism was also involved in resolution of rotavirus infection in mice.

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SUMMARYOral tolerance has been characterized as an immunological hyporesponsiveness to fed antigen. Previous studies have suggested that high-dose oral tolerance involves the preferential interaction of B7 with CTLA-4 on the T cell. To determine whether similar mechanisms are involved in the induction of lowdose oral tolerance, mice were treated with anti-CTLA-4 monoclonal antibody (MoAb), with or without IL-12, at the time of feeding. Results showed that anti-CTLA-4 MoAb alone failed to restore cellular proliferation, antibody titres and IFN-g levels; however, IL-4 cytokine levels in OVA-fed mice were partially restored. In contrast, administration of IL-12 along with anti-CTLA-4 MoAb to mice during feeding completely prevented the suppression of Th1 immune responses, as shown by increased serum IgG2a titres, IFN-g production and cell proliferation. These results suggest that blocking B7-CTLA-4 interactions in the presence of IL-12 prevents the induction of low-dose oral tolerance at the Th1 cell level.