Characterization of Multiple Cytokine Combinations and TGF-beta on Differentiation and Functions of Myeloid-Derived Suppressor Cells

Abstract

Myeloid-derived suppressor cells (MDSCs) regulate T cell immunity, and this population is a new therapeutic target for immune regulation. A previous study showed that transforming growth factor-beta (TGF-beta) is involved in controlling MDSC differentiation and immunoregulatory function in vivo. However, the direct effect of TGF-beta on MDSCs with various cytokines has not previously been tested. Thus, we examined the effect of various cytokine combinations with TGF-beta on MDSCs derived from bone marrow cells. The data show that different cytokine combinations affect the differentiation and immunosuppressive functions of MDSCs in different ways. In the presence of TGF-beta, interleukin-6 (IL-6) was the most potent enhancer of MDSC function, whereas granulocyte colony-stimulating factors (G-CSF) was the most potent in the absence of TGF-beta. In addition, IL-4 maintained MDSCs in an immature state with an increased expression of arginase 1 (Arg1). However, regardless of the cytokine combinations, TGF-beta increased expansion of the monocytic MDSC (Mo-MDSC) population, expression of immunosuppressive molecules by MDSCs, and the ability of MDSCs to suppress CD4(+) T cell proliferation. Thus, although different cytokine combinations affected the MDSCs in different ways, TGF-beta directly affects monocytic-MDSCs (Mo-MDSCs) expansion and MDSCs functions.