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. Treg, 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-gamma (IFN-gamma) and IL-17 were analysed using ELISA for protein and quantitative RT-PCR for mRNA. T-reg down-regulated the secretion of both IFN-gamma (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-gamma 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