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

Am J Clin Nutr. 2004 Dec;80(6):1618-25. doi: 10.1093/ajcn/80.6.1618.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD28 Antigens / immunology
  • CD3 Complex / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / microbiology
  • Case-Control Studies
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Crohn Disease / drug therapy
  • Crohn Disease / immunology*
  • Crohn Disease / metabolism
  • Cytokines / biosynthesis*
  • Dendritic Cells / metabolism*
  • Dendritic Cells / microbiology
  • Dose-Response Relationship, Immunologic
  • Female
  • Flow Cytometry
  • Humans
  • Interleukin-10 / biosynthesis
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / immunology
  • Interleukin-4 / biosynthesis
  • Lactobacillus / physiology*
  • Male
  • Middle Aged
  • Monocytes / immunology
  • Monocytes / metabolism
  • Probiotics* / administration & dosage

Substances

  • CD28 Antigens
  • CD3 Complex
  • Cytokines
  • Interleukin-2
  • Interleukin-10
  • Interleukin-4