CD4 + CD25 + Regulatory T Cells Modulate the T-Cell and Antibody Responses in Helicobacter -Infected BALB/c Mice

Abstract

ABSTRACT Gastric Helicobacter spp. induce chronic gastritis that may lead to ulceration and dysplasia. The host elicits a T helper 1 (Th1) response that is fundamental to the pathogenesis of these bacteria. We analyzed immune responses in Helicobacter -infected, normal mice depleted of CD4 + CD25 + T cells to investigate the in vivo role of regulatory T cells (Tregs) in the modulation of Helicobacter immunopathology. BALB/c and transgenic mice were depleted of CD4 + CD25 + T cells by administration of an anti-CD25 antibody either at the time of infection with Helicobacter or during chronic infection and gastritis. Depletion of CD25 + Tregs prior to and during infection of mice with Helicobacter spp. did not affect either bacterial colonization or severity of gastritis. Depletion of CD25 + Tregs was associated with increased Helicobacter -specific antibody levels and an altered isotype distribution. Paragastric lymph node cells from CD25 + Treg-depleted and control infected mice showed similar proliferation to Helicobacter antigens, but only cells from anti-CD25-treated animals secreted Th2 cytokines. CD25 + Tregs do not control the level of gastritis induced by gastric Helicobacter spp. in normal, thymus-intact BALB/c mice. However, CD25 + Tregs influence the cytokine and antibody responses induced by infection. Autoimmune gastritis is not induced in Helicobacter -infected mice depleted of CD25 + Tregs but is induced in CD25 + Treg-depleted mice, which have a higher frequency of autoreactive T cells.