Lactose differentially modulates functionalities of antigen-presenting cells and T cells

Abstract

Abstract Lactose is a milk sugar that appears to have immunomodulatory properties, but conflicting reports are available regarding its effects on inflammatory response and Treg cell functions. To delineate these aspects, we sought to test the hypothesis that lactose alters T-cell responses by modulating the functionalities of antigen-presenting cells (APCs). First, using the mouse macrophage cell line (RAW 264.7), we noted that lactose could reduce LPS-induced oxidative stress (P>0.05) without altering viability. Second, while the expression of MHC class II molecule was unchanged, an inverse relationship was noted with the costimulatory molecules [downregulated CD40 (P>0.005) and CD80 (P>0.005), and upregulated CD86 (P>0.005)], suggesting that lactose-mediated effects on APCs are heterogeneous and may involve unique regulatory elements for individual gene expression. Third, by testing the effects of lactose in the sorted mouse primary T cells, lactose moderately modulates T cell activation stimulated by anti-CD3 and anti-CD28, including IL-2 and IFN-γ production, but the cell viability was unaffected. However, upon the addition of IL-2, the reduced T cell activation was no longer apparent as evaluated by CFSE staining of CD4 and CD8 T cells, indicating that lactose’s effects on T cells may involve an IL-2-dependent mechanism. Taken together, our data support the notion that lactose could exert its effects on T cells directly or indirectly by modulating the APC functions that may have implications on health and disease.