Ginsenoside compound K suppresses the abnormal activation of T lymphocytes in mice with collageninduced arthritis

Aim： To investigate the anti-arthritis and immunomodulatory activities of ginsenoside compound K （C-K） in mice with collagen-induced arthritis （ClA）. Methods： DBA/1 mice with ClA were treated with C-K （28, 56 or 112 mg.kg-l.d-1, ig） or the positive control methotrexate （2 mg/kg, ig, every 3 d） for 34 d. Splenic T and B lymphocytes were positively isolated using anti-CD3-coated magnetic beads or a pan B cell isolation kit. T lymphocyte subsets, and CD28, T cell receptor （TCR）, cytotoxic T lymphocyte-associated antigen-4 （CTLA-4） and programmed death-1 （PD-1） expression in purified splenic T lymphocytes were analyzed using flow cytometry, Western blotting and laser confocal microscopy. Results： C-K treatment significantly ameliorated the pathologic manifestations of ClA mice, remarkably inhibited T lymphocyte proliferation, and marginally inhibited the proliferation of B lymphocytes. C-K treatment significantly suppressed TNF-α and anti- Cll antibody levels, and increased IFN-y level in the joints of CIA mice, but did not alter IL-4 production. Treatment of CIA mice with C-K significantly decreased the percentages of activated T cells, co-stimulatory molecule-expressing T cells and effector memory T cells, and increased the frequencies of naive T cells and regulatory T cells. Furthermore, C-K treatment significantly decreased the expression of CD28 and TCR, whereas it increased the expression of CTLA-4 and PD-1 on T lymphocytes of ClA mice. Methotrexate treatment exerted comparable effects in all these experiments. Conclusion： C-K suppresses the progression of ClA through regulating TCR, CD28, CTLA-4 and PD-1 expression, thus inhibiting the abnormal activation and differentiation of T lymphocytes.