Bifidobacteria BbC50 Fermentation Products Induce Human Cd4+ Regulatory T Cells with Antigen-Specific Activation and Bystander Suppression

Probiotic bacteria have been shown to have health benefits in various situations (inflammation, allergy, infection). We previously showed that a bacteria-free fermentation product of Bifidobacterium breve C50 (BbC50sn) induced high IL-10 secretion by human dendritic cells. As IL-10 is a regulatory cytokine, the aim of the present study was to examine whether DCs cultured in the presence of BbC50sn could induce regulatory T cells in an allogeneic context. Purified CD4(+)CD25(-) human T cells were co-cultured with allogeneic BbC50sn-treated dendritic cells for 4 weeks. The T cell population (BbC50sn-T) was analysed both at phenotypical and functional [ability to inhibit a mixed lymphocyte reaction (MLR)] levels. We showed that T lymphocytes acquired phenotype characteristics of regulatory T cells after 4 weeks of co-culture with BbC50sn-DCs, and inhibited in vitro T lymphocyte proliferation and IFN-gamma production in an MLR. Transwell experiments demonstrated that this suppressive activity was not T cell contact-dependent but probably mediated by a soluble factor. Although BbC50sn-T cells secreted significant amounts of IL-10 and TGF-beta, their suppressive effect is most likely not mediated through these cytokines. This is, to our knowledge, the first demonstration of in vitro regulatory T cell induction by a bacteria-free fermentation product in an allogeneic context.