Oral administration of PSK can improve the impaired anti-tumor CD4+ T-cell response in gut-associated lymphoid tissue (GALT) of specific-pathogen-free mice.
We investigated both the effect and the mechanism of oral (p.o.) administration of PSK, a protein-bound polysaccharide derived from Basidiomycetes, on the anti-tumor T-cell response in gut-associated lymphoid tissue (GALT). The p.o. administration of PSK significantly suppressed the growth of colon 26 carcinoma (C-26) inoculated into the subserosal space of the cecum (i.c.), and augmented the tumor-neutralizing activity of the draining mesenteric lymph node (LN) cells. PSK treatment also significantly decreased the levels of immunosuppressive factors such as plasma transforming growth factor (TGF)-beta in the i.c. C-26-inoculated mice. We also evaluated the improving effect of PSK on the anti-tumor T-cell response in GALT by utilizing B7-transfected P815 mastocytoma (B7/P815). The PSK treatment promoted the rejection of i.c.-inoculated B7/P815 and restored the CD4+ T-cell-dependent proliferative response of the draining mesenteric LN cells against in vitro restimulation. Furthermore, the treatment also decreased the TGF-beta production but increased the IFN-gamma production of these cells. The p.o. administration of PSK, however, showed no effect in the CD8+ T-cell-dependent cytolytic activity of the draining mesenteric LN cells after in vitro restimulation. Overall, these results indicate that the p.o. administration of PSK can improve the impaired anti-tumor CD4+ T-cell response in GALT, mainly through a suppression of TGF-beta production and a restoration of IFN-gamma production.
Harada
M
M
Department of Virology, Kyushu University, Fukuoka, Japan. harada@bioreg.kyushu-u.ac.jo
Matsunaga
K
K
Oguchi
Y
Y
Iijima
H
H
Tamada
K
K
Abe
K
K
Takenoyama
M
M
Ito
O
O
Kimura
G
G
Nomoto
K
K
D000284:Administration, Oral; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D003110:Colonic Neoplasms / Q000097:blood / Q000276:immunology*; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000494:pharmacology*; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000378:metabolism; D008198:Lymph Nodes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008643:Mesentery; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D011509:Proteoglycans / Q000008:administration & dosage / Q000494:pharmacology*; D013047:Specific Pathogen-Free Organisms; D016212:Transforming Growth Factor beta / Q000097:blood
D000903:Antibiotics, Antineoplastic; D007155:Immunologic Factors; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; C010770:polysaccharide-K; D007371:Interferon-gamma