High mobility group box chromosomal protein 1 acts as a proliferation signal for activated T lymphocytes

The nuclear protein high mobility group box chromosomal protein 1 (HMGB1) can be translocated extracellularly and plays a well-established role as a pro-inflammatory mediator during innate immune responses. Much less is known about the role of HMGB1 in adaptive immunity, since only a few studies have addressed the issue. We herein activated subsets of purified, primary human T lymphocytes with solid-phase bound anti-CD3 mAb and assessed the effects of recombinant HMGB1 protein on cell proliferation when added to the cultures. HMGB1 acted as a proliferative signal for human T cells during suboptimal anti-CD3 mAb stimulation. Statistically significant increased proliferation was recorded in both CD4+ and CD8+ T-cell cultures at HMGB1 concentrations ranging from 0.25 to 1.0 microg/ml. HMGB1 had no effect on proliferation in the absence of anti-CD3 stimulation or during T-cell activation obtained using high doses of anti-CD3 mAb. Our results demonstrate a direct HMGB1-mediated effect in adaptive immunity.