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

Abstract

GastricHelicobacterspp. 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 inHelicobacter-infected, normal mice depleted of CD4⁺CD25⁺T cells to investigate the in vivo role of regulatory T cells (Tregs) in the modulation ofHelicobacterimmunopathology. 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 withHelicobacteror during chronic infection and gastritis. Depletion of CD25⁺Tregs prior to and during infection of mice withHelicobacterspp. did not affect either bacterial colonization or severity of gastritis. Depletion of CD25⁺Tregs was associated with increasedHelicobacter-specific antibody levels and an altered isotype distribution. Paragastric lymph node cells from CD25⁺Treg-depleted and control infected mice showed similar proliferation toHelicobacterantigens, but only cells from anti-CD25-treated animals secreted Th2 cytokines. CD25⁺Tregs do not control the level of gastritis induced by gastricHelicobacterspp. in normal, thymus-intact BALB/c mice. However, CD25⁺Tregs influence the cytokine and antibody responses induced by infection. Autoimmune gastritis is not induced inHelicobacter-infected mice depleted of CD25⁺Tregs but is induced in CD25⁺Treg-depleted mice, which have a higher frequency of autoreactive T cells.