Participation of endogenously produced interferon gamma in interleukin 4-mediated tumor rejection.
To elucidate the molecular mechanism underlying IL-4-induced tumor rejection, we challenged mice with a mouse adenocarcinoma cell line, colon 26, genetically engineered to express constitutively IL-4 gene (colon 26/IL-4). Immunocompetent BALB/c mice rejected colon 26/IL-4 cells but not parental cells or cells transduced with a control gene (colon 26/control). Moreover, on rechallenge, parental cells and colon 26/control cells were rejected by normal BALB/c mice that had previously rejected colon 26/IL-4. However, both nude and severe combined immunodeficiency (SCID) mice failed to reject colon 26/IL-4 as well as parental or colon 26/control cells. In contrast, nude mice did reject colon 26/IL-4 after transfer of lymphocytes obtained from the draining lymph nodes of BALB/c mice injected with colon 26/IL-4. These results indicate that challenging mice with colon 26/IL-4 tumor cells resulted in the generation of memory cytotoxic T lymphocytes in the draining lymph nodes. At 3 days after the challenge, IFN-gamma, IL-12 p35, and p40 mRNA expression was selectively enhanced in the draining lymph nodes of mice bearing colon 26/IL-4 cells. Finally, mice deficient in the IFN-gamma gene did not reject colon 26/IL-4 cells. These results suggest that IL-4-induced memory cytotoxic T lymphocyte generation requires IFN-gamma production in the draining lymph nodes, in order to generate a protective immune response.
Nishihori
H
H
Department of Molecular Oncology, Cancer Research Institute, Kanazawa University, Japan.
Tsuji
H
H
Wang
H
H
Tahara
H
H
Akiyama
M
M
Ogawa
Y
Y
Matsushima
K
K
Iwakura
Y
Y
Mukaida
N
N
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000818:Animals; D002455:Cell Division / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006084:Graft Rejection / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D018664:Interleukin-12 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D012333:RNA, Messenger; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D007074:Immunoglobulin G; D012333:RNA, Messenger; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma