HMGN2: An Antitumor Effector Molecule of γδT Cells.

T cells function in the regulation of T-cell activation in cancer and have been identified as a novel target for cancer immunotherapy. Activated T cells release a series of cytotoxic molecules-including granulysin, perforin, Fas/Fas ligand (Fas-L), and granzymes A and B-to kill target cells. Our previous research has shown that high mobility group nucleosomal-binding domain 2 (HMGN2), which is expressed at a high level in activated CD8(+)T cells, is an antitumor effector molecule of CD8(+)T cells. In the present study, we examined the expression and antitumor effects of HMGN2 in T cells. Peripheral blood mononuclear cells (PBMCs) were isolated from healthy donors with a PBMC separation column. PMBCs were stimulated with isopentenyl pyrophosphate (IPP) and interleukin-2 (IL-2) for 10 days for activation and expansion. Activated T cells were isolated from IPP-pretreated PBMCs with a Moflo XDP flow cytometry sorter. The expression of HMGN2 in T cells was detected by flow cytometry and enzyme-linked immunosorbent assay. The cytotoxic effects of T cells and HMGN2 were analyzed by carboxyfluorescein succinimidyl ester labeling. IPP combined with IL-2 induced significant activation and expansion of T cells in vitro. HMGN2 was constitutively expressed in T cells. IPP-activated T cells expressed a high level of HMGN2 that could be detected intracellularly and in the supernatant. Moreover, supernatants of purified T cells were sufficient to kill tumor cells and could be blocked with anti-human HMGN2 antibody. This study suggests that HMGN2 is an antitumor effector molecule of T cells.