HMGN2, a new anti-tumor effector molecule of CD8⁺ T cells.

Abstract

BACKGROUND:

Cytolytic T lymphocytes (CTL) and natural killer (NK) cells have been implicated as important cells in antitumor responses. Our previous research has shown that high mobility group nucleosomal-binding domain 2 (HMGN2) could be released by IL-2 and PHA stimulated peripheral blood mononuclear cells (PBMCs) and also induced tumor cells apoptosis at low doses. In this study, we isolated and cultured PBMCs and CD8⁺ T cells to analyze the expression and antitumor effects of HMGN2.

METHODS:

PBMCs from healthy donors were isolated using Human Lymphocyte Separation tube. CD8⁺ T cells were separated from the PBMCs using MoFlo XDP high-speed flow cytometry sorter. Activation of PBMCs and CD8⁺ T cells were achieved by stimulating with Phytohemagglutinin (PHA) or tumor antigen. In addition, the methods of ELISA, intracellular staining, and fluorescence-labeling assays were used.

RESULTS:

PHA induced PBMCs to release high levels of HMGN2, and CD8⁺ T cells was the major cell population in PBMCs that release HMGN2 after PHA activation. Tumor antigen-activated CD8⁺ T cells also released high levels of HMGN2. Supernatants of tumor antigen-activated CD8⁺ T cells were able to kill tumor cells in a dose-dependent manner. This antitumor effect could be significantly blocked by using an anti-HMGN2 antibody. Fluorescence-labeling assays showed that the supernatant proteins of activated CD8⁺ T cells could be transported into tumor cells, and the transport visibly decreased after HMGN2 was depleted by anti-HMGN2 antibody.

CONCLUSIONS:

These results suggest that HMGN2 is an anti-tumor effector molecule of CD8⁺ T cells.

• Authors: Lin Su, Ankang Hu, Yang Luo, Wenjie Zhou, Ping Zhang, Yun Feng
• Journal: Molecular cancer (Mol Cancer) Vol. 13 Pg. 178 (Jul 25 2014) ISSN: 1476-4598 [Electronic] England
• PMID: 25060707 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• HMGN2 Protein
• Phytohemagglutinins

Topics

• Antigens, Neoplasm (immunology)
• CD8-Positive T-Lymphocytes (metabolism)
• Cell Line, Tumor
• Cytotoxicity, Immunologic (drug effects)
• HMGN2 Protein (metabolism)
• Humans
• Lymphocyte Activation (drug effects)
• Neoplasms (immunology)
• Phytohemagglutinins (pharmacology)
• Protein Transport (drug effects)