Antigen-specific in vitro suppression of murine Helicobacter pylori-reactive immunopathological T cells by CD4+CD25+ regulatory T cells

A Helicobacter pylori-specific in vitro coculture system was established and used to study the role of CD4(+)CD25(+) regulatory T cells (Treg) in gastritis development in mice with H. pylori infection. Effects of therapeutic immunization against H. pylori infection on the Treg function were also studied to better understand the mechanisms leading to postimmunization gastritis in these mice. Depletion of Treg led to extensive proliferation to H. pylori antigens of CD4(+) T cells isolated from either naive, H. pylori-infected or H. pylori-immunized mice. Using the Treg-depleted CD4(+) T cells from immunized mice as effector cells, we compared the suppressive efficacy of Treg isolated from naive, infected or immunized mice and found that Treg from naive mice, and slightly less efficiently from infected mice, suppressed the CD25(-) effector T-cell response and in most cases were distinctly more efficacious than Treg isolated from immunized mice. The suppressive efficacy of Treg isolated from the differently treated mice correlated closely with production of interleukin-5 (IL-5) by the Treg and suppression of interferon-gamma and IL-2 production by the CD25(-) effector T cells. Our study is the first to demonstrate in H. pylori-induced chronic infection, antigen-specific Treg with differential efficacy in suppressing H. pylori proinflammatory T effector cells.