CD4 super(+) T-cell responses and distribution at the colonic mucosa during Brachyspira hyodysenteriae-induced colitis in pigs

The spirochaete Brachyspira hyodysenteriae causes swine dysentery, a severe colitis characterized by mucosal enlargement as a result of crypt elongation and epithelial necrosis. Most efforts to understand the pathogenesis of this disease have focused on the aetiological agent and its virulence factors. However, the host immune response has been considered an important factor in disease development. Previous research has shown that B. hyodysenteriae induces systemic CD4 super(+) and gamma delta T-cell responses after intramuscular immunization. Here, we have evaluated changes in the CD4 super(+) and gamma delta T-cell composition and distribution the different compartments of the colonic mucosa of pigs challenged with B. hyodysenteriae. We report that, in infected pigs, gamma delta T cells were significantly depleted from the epithelial layer, although their numbers were maintained in the lamina propria. In addition, CD4 super(+) T cells aggregated in clusters located in the lamina propria and submucosa. Ex vivo analyses of CD4 super(+) T-cell responses to B. hyodysenteriae antigens correlated with the changes in the mucosal CD4 super(+) T-cell distribution observed in infected pigs; CD4 super(+) T cells recovered from peripheral blood and colonic lymph nodes of infected pigs proliferated to B. hyodysenteriae antigens, whereas no differences were found in the gamma delta T-cell responses between challenged and control groups. In addition, colonic lymph node CD4 super(+) T cells had a predominant memory-activated phenotype. These results indicate that infection with B. hyodysenteriae induces a mucosal CD4 super(+) T-cell response and points to CD4 super(+) T cells being important contributors to the immunopathogenesis of swine dysentery.