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

摘要

In pigs, αβ CD4+ and γδ 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 αβ CD4+ and γδ 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 γδ 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 γδ T cells to B. hyodysenteriae antigens. Results show that while the proliferative responses of CD4+ were exclusively antigen-specific, γδ 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-γ production indicated that CD4+ T cells are the major source of this cytokine, although stimulation with B. hyodysenteriae antigens decreased IFN-γ-producing CD4+ T cells. This effect was paralleled by an increase in γδ T cells producing IFN-γ. These results suggest that, as has been demonstrated for other infectious disease models, γδ 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 γδ T cells; however, vaccination ameliorated the loss of this lymphocyte subset. These cellular changes were accompanied by modulation of cytokine expression. Particularly, TNF-α, IL-1β and TGF-β₁ mRNA were upregulated in vaccinated and infected pigs. The possible contribution of porcine CD4+ and γδ 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.