Enhancing effect of PS-K on IL-2-induced lymphocyte activation: possible involvement of antagonistic action against TGF-beta.
Effects of protein-bound polysaccharide (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.
Yamaguchi
Yoshiyuki
Y
Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan. shogo@hiroshima-u.ac.jp
Minami
Kazuhito
K
Ohshita
Akiko
A
Kawabuchi
Yoshiharu
Y
Noma
Kosuke
K
Toge
Tetsuya
T
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D004357:Drug Synergism; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D020014:K562 Cells; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D009369:Neoplasms / Q000097:blood / Q000276:immunology* / Q000628:therapy; D011509:Proteoglycans / Q000494:pharmacology*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D000276:Adjuvants, Immunologic; D007376:Interleukin-2; D011509:Proteoglycans; D015375:Receptors, Interleukin-2; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; C010770:polysaccharide-K; D019098:Telomerase