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

Background: 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. Objective: We determined whether Lactobacillus rhamnosus can modulate T cell responses in vitro and in vivo. Design: 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. Results: 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. Conclusions: 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.