Date of Graduation


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This research has focused on the regulation of mucosal and systemic humoral immune responses to respiratory enteric orphan virus (reovirus). Enteric infection with reovirus elicits both intestinal and systemic humoral immunity characterized by the production of local mucosal IgA and systemic serum IgG. Although the immune responses to reovirus have been well described, the events that regulate immunity are less understood. We observed that the quality of the humoral immune response to enteric reovirus infection was influenced by genetic background and route of viral infection. Specifically, mice of the H-2{dollar}\\sp{lcub}\\rm d{rcub}{dollar} MHC haplotype were shown to generate T helper 2-associated antibody responses following intradermal, but not oral reovirus infection. This route-dependent response occurred in the absence of obvious differences in cytokine production in mucosal and systemic lymphoid tissues and was associated with the viral dose. In addition to the route of infection, we also investigated the role of CD8{dollar}\\sp+{dollar} T cells in regulating mucosal and systemic humoral immunity. We demonstrated that in the absence of conventional CD8{dollar}\\sp+{dollar}, {dollar}\\alpha{dollar}/{dollar}\\beta{dollar} T cell receptor{dollar}\\sp+{dollar}T cells, {dollar}\\beta{dollar}2-microglobulin-deficient mice have enhanced virus-specific IgA and IgG responses following oral reovirus infection, which may be related to increased T helper cell activity. These data demonstrate that CD8{dollar}\\sp+{dollar} T cells may down regulate the humoral and T helper cell immune responses following enteric virus infection. These studies are significant because they have furthered our understanding of the dynamic relationship between the mucosal and systemic immune systems following enteric reovirus infection. We have shown that factors such as genetic predisposition, route of antigen administration and antigen dose can have regulatory effects on the antibody response to enteric viruses. In addition, our studies suggest that humoral immunity to enteric virus infection can be sufficiently protective in the absence of conventional CD8{dollar}\\sp+{dollar} T cells. This type of information is applicable to the development of efficient vaccine strategies to promote mucosal and systemic immunity of the necessary quality and magnitude to provide protection.