CD4+ T Cells Transfer Resistance Against Citrobacter rodentium‐Induced Infectious Colitis by Induction of Th 1 Immunity

Abstract

Citrobacter rodentium induces an acute, self-limited colitis in mice which is histologically associated with crypt hyperplasia. The infection serves as a model for human infectious colitis induced by enteropathogenic Escherichia coli. We investigated if Balb/c mice, which had spontaneously cleared C. rodentium infection, were protected against re-infection and if resistance against intestinal infection can be systemically transferred using spleen cells. The course of infection was monitored by faecal excretion. Spleen cells, splenic CD3+ and CD4+ cells were transferred from resistant mice to non-infected recipients prior to infection. Cytokine secretion, serum and faecal antibody titres and histological disease severity were assessed. Balb/c mice were resistant against re-infection. The course of infection was shorter in mice receiving primed spleen cells, CD3+ and CD4+ cells. Transfer of CD4+ T cells from resistant mice induced gamma-interferon, interleukin (IL)-2 and IL-17 secretion and suppressed IL-10 secretion. Anti-Citrobacter serum IgG1 and IgG2a enzyme-linked immunosorbent assay OD levels were increased. Faecal IgA secretion was increased while serum IgA was suppressed in recipients of CD4+ cells. Large bowel histology showed protection from colitis in recipients of primed cells as indicated by normal colonic epithelium. In Balb/c mice, C. rodentium infection is followed by resistance, which can be transferred by CD4+ cells. Transfer of protection is associated with IL-17 secretion, enhanced serum IgG and faecal IgA secretion. This is the first study to demonstrate the mechanisms by which systemic resistance from previously C. rodentium-infected mice can be transferred to non-infected animals.