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
beta 2-microglobulin (beta 2m) knockout mice with murine rotavirus. Naive beta 2m knockout mice shed rotavirus
antigen 2 days longer than did normal control mice but completely resolved primary
infection. beta 2m knockout naive mice treated with depleting doses of an anti-CD8
monoclonal antibody before
infection shed
viral antigen for an additional day. Upon rechallenge, beta 2m knockout mice, either treated with the anti-CD8 antibody or not treated, were completely resistant to
reinfection. Clearance of
rotavirus infection in naive beta 2m knockout mice correlated with the development of intestinal rotavirus-specific
immunoglobulin A. Before rechallenge, beta 2m 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 JHD knockout mice. After primary
infection, most naive JHD mice had similar virus-shedding clearance curves as did control mice and completely resolved primary
infection. However, 2 of 29 became chronically infected. All JHD mice treated with anti-CD8 antibody became chronically infected with murine rotavirus. Upon rechallenge, JHD 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.