Lactose inhibits regulatory T-cell-mediated suppression of effector T-cell interferon-γ and IL-17 production

Our interest in lactose as an immunomodulatory molecule results from studies showing that lactose binds to galectin-9, which has been shown to have various regulatory functions in the immune system including regulation of T-cell responses. Impaired regulation of T helper (Th)1 and Th17 type immune responses and dysfunction of regulatory T cells (T(reg)) have been implicated in many human immune-mediated diseases. In the present study, we investigated the effects of lactose on immune regulation using co-cultures of human peripheral blood mononuclear cell (PBMC)-derived T(reg) and effector T cells (T(eff)) obtained from twenty healthy adults. T(reg), i.e. CD4(+)CD25(+)CD127(−), were isolated from PBMC by immunomagnetic separation. The fraction of CD4(+)CD127(−) cells that was depleted of CD25(+) cells was used as T(eff). T(reg) and T(eff) at a ratio 1:5 were activated and the effects of lactose on the secretion of interferon-γ (IFN-γ) and IL-17 were analysed using ELISA for protein and quantitative RT-PCR for mRNA. T(reg) down-regulated the secretion of both IFN-γ (8·8–3·9 ng/ml, n 20, P= 0·003) and IL-17 (0·83–0·64 ng/ml, n 15, P= 0·04) in co-cultures, while in the presence of lactose the levels of secreted IFN-γ and IL-17 remained high and no down-regulation was observed (16·4 v. 3·99 ng/ml, n 20, P< 0·0001, and 0·74 v. 0·64 ng/ml, n 15, P= 0·005, respectively). We showed that lactose inhibits human T(reg)-mediated suppression of Th1 and Th17 immune responses in vitro.