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

Abstract

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 ␤ 2-microglobulin (␤ 2 m) knockout mice with murine rotavirus. Naive ␤ 2 m knockout mice shed rotavirus antigen 2 days longer than did normal control mice but completely resolved primary infection. ␤ 2 m knockout naive mice treated with depleting doses of an anti-CD8 monoclonal antibody before infection shed viral antigen for an additional day. Upon rechallenge, ␤ 2 m knockout mice, either treated with the anti-CD8 antibody or not treated, were completely resistant to reinfection. Clearance of rotavirus infection in naive ␤ 2 m knockout mice correlated with the development of intestinal rotavirus-specific immunoglobulin A. Before rechallenge, ␤ 2 m 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.

Intranasal delivery of whole cell lysate of Mycobacterium tuberculosis induces protective immune responses to a modified live porcine reproductive and respiratory syndrome virus vaccine in pigs

“…Apart from the effective humoral response, robust CMI response is critical for protective PRRSV immunity [8,56,57,62,63]. Pathogen specific mucosal CD8 + T cells are required for the clearance of intracellular pathogens at both enteric and respiratory mucosal sites [64][65][66]. Consistent with those details, in PRRS-MLV+ Mtb WCL received pigs there was an increased frequency of CD8 + T cells and secretion of Th1 cytokines in pig lungs.…”

Evaluation of immune responses to porcine reproductive and respiratory syndrome virus in pigs during early stage of infection under farm conditions

“…Lymphocytes expressing the CD8 marker are important in viral clearance by secreting IFN-γ and mediating pathogen-specific cytotoxicity [21,22]. Pigs have abundant CD4 + CD8 + T cells and these cells possess memory, T-helper, and cytolytic properties, and are called as "Th/memory cells," and they too secrete IFN-γ [21,23].…”

“…The Th2 cytokine IL-4 is involved in suppression of pathogen-specific Th1 immune responses [17,18], but the role of IL-4 in the pig immune system appears to be different [19,20]. Lymphocytes expressing markers CD4 or CD8 alone and CD4 and CD8 together are important in viral clearance by secreting IFN-γ and mediating pathogen specific cytotoxicity [21][22][23][24]. Foxp3expressing CD4 + CD25 + cells with immunosuppressive properties, called "T-regulatory cells (Tregs)", have been identified in pigs [25].…”

Viral Infections of Laboratory Mice

“…Successful viral control and clearance is promoted by an intact immune response [396][397][398][399], and some immunodeficient mice (e.g. Prkdc scid and Rag2 tm1Fwa mice) may shed virus for extended periods or become persistently infected [400,401]. Protection against MuRV-A/EDIM reinfection is primarily mediated by antibodies [396,397].…”