Role of B cells and cytotoxic T lymphocytes in clearance of and immunity to rotavirus infection in mice

The immune mechanisms involved in clearance of and immunity to rotavirus infection are poorly understood. Although mice with severe combined immunodeficiency (SCID mice) become chronically infected, nude mice have been reported to clear rotavirus infection similarly to immunocompetent controls. To better characterize the role of cytotoxic T lymphocytes (CTLs) in clearance of and immunity to rotavirus infection, we infected naive or previously infected β₂-microglobulin (β₂m) knockout mice with murine rotavirus. Naive β₂m knockout mice shed rotavirus antigen 2 days longer than did normal control mice but completely resolved primary infection. β₂m knockout naive mice treated with depleting doses of an anti-CD8 monoclonal antibody before infection shed viral antigen for an additional day. Upon rechallenge, β₂m knockout mice, either treated with the anti-CD8 antibody or not treated, were completely resistant to reinfection. Clearance of rotavirus infection in naive β₂m knockout mice correlated with the development of intestinal rotavirus-specific immunoglobulin A. Before rechallenge, β₂m knockout mice had high levels of intestinal rotavirus- specific immunoglobulin A. These findings suggest that CTLs mediate rotavirus clearance but are not required for this function and that CTLs are not necessary for development of immunity to rotavirus reinfection. To further characterize the effector mechanisms involved in clearance and prevention of rotavirus infection, similar studies were performed with B-cell-deficient J(H)D knockout mice. After primary infection, most naive J(H)D mice had similar virus-shedding clearance curves as did control mice and completely resolved primary infection. However, 2 of 29 became chronically infected. All J(H)D mice treated with anti-CD8 antibody became chronically infected with murine rotavirus. Upon rechallenge, J(H)D mice which had cleared primary infection were all susceptible to reinfection. These findings suggest that B cells also play a role in clearance of primary infection but are absolutely necessary for development of immunity against rotavirus reinfection.