Decrease of the regulatory T-cell population by adoptive T-cell transfer in a mouse colorectal cancer transplant model.
We examined the effects of adoptive T-cell transfer (ACT) on the population of regulatory T cells (Tregs) in a mouse colorectal cancer transplant model. In an in vivo study, Treg populations in Balb/c mice colon26 transplant model after ACT were analyzed in peripheral blood, local lymph node, and tumor. In an in vitro study CD4+ cells were cultured in medium containing TGF-beta to induce Tregs. LAK cells were added or not in this Treg induction system. Treg induction after coculture with LAK was investigated. We also studied the role of IFN-gamma in the mechanism of Treg induction. Tregs in the draining lymph nodes and tumor were significantly suppressed by ACT. The induction of Tregs in vitro was inhibited by coculture with LAK cells. Furthermore, Tregs in the cultured cells were significantly inhibited by addition of exogenous IFN-gamma. Moreover, Tregs were increased by addition of IFN-gamma mAb. ACT may decrease Tregs in tumor-bearing hosts. One of the mechanisms is considered to be IFN-gamma inhibiting the induction of Tregs.
Department of Molecular Gastroenterology & Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Tsuguhiro
T
Matsumoto
Satoshi
S
Kokura
Takeshi
T
Ishikawa
Jun
J
Funaki
Satoko
S
Adachi
Koji
K
Mori
Naoyuki
N
Sakamoto
Kazuhiro
K
Katada
Kazuhiro
K
Kamada
Nobuaki
N
Yagi
Osamu
O
Handa
Tomohisa
T
Takagi
Kazuhiko
K
Uchiyama
Yuji
Y
Naito
Toshikazu
T
Yosikawa
D000230:Adenocarcinoma / Q000276:immunology* / Q000517:prevention & control; D019264:Adoptive Transfer; D000818:Animals; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D003110:Colonic Neoplasms / Q000276:immunology* / Q000517:prevention & control; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors; D007124:Immunoenzyme Techniques; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology / Q000637:transplantation*; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma