IL-35 inhibits CD8+ T cells activity by suppressing expression of costimulatory molecule CD28 and Th1 cytokine production

Background: Interleukin-35 (IL-35), a novel immune-suppressing cytokine, can promote tumor angiogenesis and inhibits anti-tumor cytotoxic lymphocyte response. Here, we aimed to investigate the potential mechanism of the effects of IL-35 on anti-tumor cytotoxic lymphocyte. Methods: Dendritic cells (DCs) were used to induce anti-tumor cytotoxic lymphocyte. Flow cytometry, carboxyfluorescein succinimidyl ester staining, ELISA assay and western blotting were used to analyze the effect of IL-35 on anti-tumor cytotoxic lymphocyte. Results: We observed that IL-35 inhibited the expression of costimulatory molecule CD28 on CD8(+) T cell surface and Th1 cytokine production. However, IL-35 did not inhibit anti-tumor cytotoxic lymphocyte proliferation nor enhance the expression of apoptosis-related proteins of anti-tumor cytotoxic lymphocyte. Moreover, IL-35 did not repress the expression of Fas ligand (FasL) on cytotoxic lymphocyte surface. Conclusions: Our findings revealed that IL-35 can inhibit CD8(+) T cells activity by suppressing the expression of costimulatory molecule CD28 and Th1 cytokine production.