Semester

Spring

Date of Graduation

2006

Document Type

Dissertation

Degree Type

PhD

College

School of Medicine

Department

Microbiology, Immunology, and Cell Biology

Committee Chair

Christopher F. Cuff.

Abstract

This work was undertaken to determine effects of routes of infection with reovirus induction of responder cytotoxic T lymphocytes (CTL). Further, this work concerns differential effects of age on humoral and CTL responses following oral and parenteral reovirus infection. Despite considerable knowledge about non-intestinal systemic viral immunity, intestinal immune response to viral infection is less understood, and it remains unknown what differences, may occur in CTL populations induced by local viral infections in the intestine or systemic periphery.;We infected mice orally or in hind footpads with reovirus, serotype 1, strain Lang (TIL), and utilized flow cytometry to assess T cell receptor (TCR) Vbeta repertoire of CD8+ cells in draining lymphoid tissues and spleens for reovirus-driven proliferative changes. We observed predominant expansion of Vbeta6+ CD8+ CTL in spleens and Peyer's patches (PP) of orally infected mice, as well as spleens and popliteal lymph nodes of footpad infected mice. Vbeta6+ CD8 + cells from orally and footpad infected mice mediated reovirus-specific cytotoxicity. TCR beta chain complementarity determining region 3beta (CDR3beta length profile analysis of Vbeta6+ CD8 + cell lines from orally and footpad infected mice, as well as cells recovered from adoptive transfer into reovirus infected SCID recipients, showed a consistent, clear, and uniform expansion of one or few clones bearing identical CDR3beta length, indicating that CTL responses following oral or parenteral infection are likely dominated by identical CTL populations.;We also compared the ability of old and young mice to mount CTL and humoral responses to reovirus. We found old and young mice had similar CTL frequency and cytotoxicity following oral and parenteral infection. We observed that while old mice mounted IgG responses to parenteral reovirus equivalent to young mice, IgA responses of orally infected aged mice were elevated compared to young mice. These data indicate old mice retain the ability to mount CTL and humoral responses against reovirus in the intestine and systemic periphery. Furthermore, old mice have potentiation of intestinal IgA responses compared to young following intestinal infection. Our results suggest the intestine can be utilized as a route of immunization to provide efficacious cell-mediated and humoral immunity in the aged.

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