Enhancing Effect of PS-K on IL-2-induced Lymphocyte Activation: Possible Involvement of Antagonistic Action Against TGF-beta

• Published in: Anticancer research 2004-03, Vol.24 (2B), p.639-647
• Main Authors: YAMAGUCHI, Yoshiyuki, MINAMI, Kazuhito, OHSHITA, Akiko, KAWABUCHI, Yoshiharu, NOMA, Kosuke, TOGE, Tetsuya
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - pharmacology; Biological and medical sciences; Cell Adhesion - drug effects; Cell Differentiation - drug effects; Cell Differentiation - immunology; Drug Synergism; Humans; Interleukin-2 - pharmacology; K562 Cells; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Medical sciences; Neoplasms - blood; Neoplasms - immunology; Neoplasms - therapy; Proteoglycans - pharmacology; Receptors, Interleukin-2 - biosynthesis; Receptors, Interleukin-2 - immunology; Receptors, Transforming Growth Factor beta - metabolism; Telomerase - metabolism; Transforming Growth Factor beta - antagonists & inhibitors; Transforming Growth Factor beta - immunology; Transforming Growth Factor beta - metabolism; Tumors; Up-Regulation - drug effects
• ISSN: 0250-7005; 1791-7530

Effects of protein-bound polysacchraide (PS)-K on interleukin (IL)-2-induced responses of peripheral blood mononuclear cells (PBMCs) were studied. PS-K (50 mcg/ml) was observed to enhance proliferative responses, cytotoxic activities against K562 and Daudi target cells, CD25+ cell population and telomerase activity of PBMCs stimulated with IL-2. The cytotoxic effector cells could be generated in the presence of PS-K even with a minimum amount of IL-2. The enhancing effect of PS-K on the IL-2-induced lymphocyte activation was more evident in PBMCs from cancer patients than in those from healthy volunteers, suggesting that PS-K may be beneficial if combined in the IL-2-based immunotherapy of cancer. TGF-beta inhibited the IL-2-induced lymphocyte activation of proliferative responses, cytotoxic activities and CD25+ cell population, the inhibitions of which were abrogated with PS-K. PS-K also abrogated the TGF-beta-induced anchorage-independent growth of normal rat kidney cells. Flow cytometric analysis using a labeled TGF-beta revealed that PS-K blocked the binding of TGF-beta at its receptor level on the surface of PBMCs. It is suggested that PS-K enhances IL-2-induced lymphocyte activation through, in part, an antagonistic action against TGF-beta.