Background: IL-15 is a homeostatic cytokine for human T and NK cells. However, whether other cytokines influence the effect of IL-15 is not known. We have studied the impact that IL-10, TGF-, IL-17A and IFN- have on the IL-15-induced proliferation of human T cells and the expression of HLA class I (HLA-I) molecules. Methods: Peripheral blood lymphocytes (PBL) were labeled with CFSE, and stimulated for 12 days with IL-15 in the absence or presence of the other cytokines. The proportion of proliferating T cells and the expression of cell surface HLA-I molecules were analyzed by flow cytometry. Results: The IL-15-induced proliferation and expansion of T cells was paralleled by an increase in the expression of HC-10-reactive HLA-I molecules, namely on T cells that underwent ≥5-6 cycles of cell division. Noteworthy, the IL-15-induced proliferation of T cells was potentiated by IL-10 and TGF-β, but not by IL-17 or IFN-, and was associated with a decrease in the expression of HC-10-reactive molecules. Conclusions: The cytokines IL-10 and TGF-β potentiate the proliferative capacity that IL-15 has on human T cells in vitro, an effect that is associated with a reduction in the amount of HC-10 reactive HLA class I molecules induced by IL-15.