Comparison of porcine CD4 and gamma-delta T cell systemic and mucosal responses to the spirochete Brachyspira hyodysenteriae

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Hontecillas-Magarzo, Raquel
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Michael J. Wannemuehler
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Veterinary Microbiology and Preventive Medicine
Our faculty promote the understanding of causes of infectious disease in animals and the mechanisms by which diseases develop at the organismal, cellular and molecular levels. Veterinary microbiology also includes research on the interaction of pathogenic and symbiotic microbes with their hosts and the host response to infection.
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In pigs, alphabeta CD4+ and gammadelta T cells constitute an important fraction of the circulating lymphocyte pool. This makes porcine an ideal animal model for functional studies of the two cell populations. A comparative evaluation of the systemic and mucosal responses of porcine alphabeta CD4+ and gammadelta T cells was conducted in the context of immunization and/or challenge with the pathogen Brachyspira hyodysenteriae. This spirochete causes a severe colitis in pigs; however, immunization with a pepsin-digested bacterin ameliorates clinical signs of disease. Protection has been associated with in vitro antigen-dependent proliferation of CD4+ and gammadelta T cells to B. hyodysenteriae antigens. A first set of experiments was conducted to evaluate the differential functional aspects of the systemic responses of CD4+ and gammadelta T cells to B. hyodysenteriae antigens. Results show that while the proliferative responses of CD4+ were exclusively antigen-specific, gammadelta T cells responded to stimuli other than B. hyodysenteriae antigens. Proliferation of the two cell populations in vitro was dependent on the presence of IL-2. In addition, examination of IFN-gamma production indicated that CD4+ T cells are the major source of this cytokine, although stimulation with B. hyodysenteriae antigens decreased IFN-gamma-producing CD4+ T cells. This effect was paralleled by an increase in gammadelta T cells producing IFN-gamma. These results suggest that, as has been demonstrated for other infectious disease models, gammadelta T cells may contribute to downregulating CD4+ T cell responses. A second study describes the impact that immunization and/or challenge had on the lymphocyte composition and cytokine environment of the colonic mucosa. Immunization decreased the colonic CD4 + T cells irrespective of the challenge status, whereas challenge with B. hyodysenteriae resulted in depletion of epithelial gammadelta T cells; however, vaccination ameliorated the loss of this lymphocyte subset. These cellular changes were accompanied by modulation of cytokine expression. Particularly, TNF-alpha, IL-1beta and TGF-beta1 mRNA were upregulated in vaccinated and infected pigs. The possible contribution of porcine CD4+ and gammadelta T cells to the development and resolution of B. hyodysenteriae-induced colitis and the mechanisms of activation of the two subsets are discussed in this dissertation in the context of the present findings.

Tue Jan 01 00:00:00 UTC 2002