Lactobacillus rhamnosus induces peripheral hyporesponsiveness in stimulated CD4+ T cells via modulation of dendritic cell function

Abstract

Although it is widely recognized that the intake of so-called probiotic microorganisms is beneficial in chronic mucosal inflammation and topical allergic disease, the immunologic details explaining how such bacteria can exert these effects remain obscure. We determined whether Lactobacillus rhamnosus can modulate T cell responses in vitro and in vivo. In vitro, human monocyte-derived dendritic cells (DCs) matured in the presence of L. rhamnosus were used to instruct naive CD4+ T cells; subsequently, the T cell response was assessed with the use of CD3/CD28 and interleukin (IL) 2. Cytokine production by ex vivo-stimulated naive cells and memory T cells was measured before and after oral supplementation with L. rhamnosus in 6 healthy volunteers and 6 patients with Crohn disease. A decreased T cell proliferation and cytokine production, especially of IL-2, IL-4, and IL-10, was observed in CD3/CD28-stimulated T cells derived from L. rhamnosus-matured DCs. This T cell hyporesponsiveness was associated with enhanced DC-T cell interaction and normal responsiveness of T cells for IL-2. In vivo oral supplementation of L. rhamnosus for 2 wk induced a similar T cell hyporesponsiveness, including impaired ex vivo T helper subsets 1 and 2 responses without up-regulation of immunoregulatory cytokines in cohorts of both healthy volunteers and patients with Crohn disease. We propose that L. rhamnosus modulates DC function to induce a novel form of T cell hyporesponsiveness; this mechanism might be an explanation for the observed beneficial effects of probiotic treatment in clinical disease.