Induction by a Lactic Acid Bacterium of a Population of CD4⁺T Cells with Low Proliferative Capacity That Produce Transforming Growth Factor β and Interleukin-10

Abstract

We investigated whether certain strains of lactic acid bacteria (LAB) could antagonize specific T-helper functions in vitro and thus have the potential to prevent inflammatory intestinal immunopathologies. All strains tested induced various levels of both interleukin-12 (IL-12) and IL-10 in murine splenocytes. In particular, Lactobacillus paracasei (strain NCC2461) induced the highest levels of these cytokines. Since IL-12 and IL-10 have the potential to induce and suppress Th1 functions, respectively, we addressed the impact of this bacterium on the outcome of CD4 ؉ T-cell differentiation. For this purpose, bacteria were added to mixed lymphocyte cultures where CD4؉ T-cells from naive BALB/c mice were stimulated weekly in the presence of irradiated allogeneic splenocytes. In these cultures, L. paracasei NCC2461 strongly inhibited the proliferative activity of CD4 ؉ T cells in a dose-dependent fashion. This was accompanied by a marked decrease of both Th1 and Th2 effector cytokines, including gamma interferon, IL-4, and IL-5. In contrast, IL-10 was maintained and transforming growth factor ␤ (TGF-␤) was markedly induced in a dose-dependent manner. The bacteria were not cytotoxic, because cell viability was not affected after two rounds of stimulation. Thus, unidentified bacterial components from L. paracasei NCC2461 induced the development of a population of CD4 ؉ T cells with low proliferative capacity that produced TGF-␤ and IL-10, reminiscent of previously described subsets of regulatory cells implicated in oral tolerance and gut homeostasis.

Ability ofLactobacillus rhamnosusGAF01 to remove AFM1in vitroand to counteract AFM1immunotoxicityin vivo

“…In rats with induced enterocolitis, the concentration of CD4 + and CD8 + cells in the intestinal lamina propria were increased to a more normal level by administration of L. plantarum (Mao et al, 1996). In another study, L. paracasei NCC2461 induced the development of a population of CD4 + T-cells with low proliferative capacity and that were induced to produce transforming growth factor (TGF)-b and interleukin (IL)-10 (von der Weid et al, 2001). In the current study, treatment with AFM 1 + L. rhamnosus GAF01 (at 1 g/kg BW) resulted in a significant improvement in immune system cell total counts (towards control levels), although in the end they were still different than control values.…”

Specific Probiotics in Enhancing Maturation of IgA Responses in Formula-Fed Infants

“…An overall trend for an increase in serum sCD14 concentrations during the first year of life, which reached statistical significance at 12 mo of age was observed. Stimulation of CD14 and TLR2 by microbial products has been demonstrated to induce TGF-␤ production in human colonic cell lines (28) and probiotic strains of lactobacilli have been reported to induce the development of T cells producing TGF-␤ in vitro (29). In addition, there are data to suggest that CD14 is required for lactobacilli to induce a response (30).…”

Preinoculation With the Probiotic Lactobacillus acidophilus Early in Life Effectively Inhibits Murine Citrobacter rodentium Colitis

“…IL-10 might also have an indirect anti-inflammatory effect because it also stimulates together with TGF-␤ IgA synthesis (40). The probiotic Lactobacillus paracasei has been shown to maintain IL-10 and induce TGF-␤ secretion by CD4ϩ T cells (41). An in vitro study has demonstrated that the incubation of the probiotic L. plantarum with mononuclear cells isolated from actively inflamed colon results in a significant increase of IL-10 (42).…”