The role of T helper type 1 (Th1) and Th2 cells in tumor immunity was investigated using Th cells induced from ovalbumin (OVA)-specific T cell receptor transgenic mice. Although Th1 cells exhibited stronger cytotoxicity than Th2 cells, both cell types completely eradicated tumors when transferred into mice bearing A20 tumor cells transfected with the OVA gene (A20-OVA). Th1 cells eradicated the tumor mass by inducing cellular immunity, whereas Th2 cells destroyed the tumor by inducing tumor necrosis. Both Th1 and Th2 cells required CD8+ T cells to eliminate tumors, and neither of these cells were able to completely eliminate A20-OVA tumors from T and B cell–deficient RAG2−/− mice. Mice cured from tumors by Th1 and Th2 cell therapy rejected A20-OVA upon rechallenge, but CD8+ cytotoxic T lymphocytes were induced only from spleen cells prepared from cured mice by Th1 cell therapy. Moreover, we demonstrated that Th1 and Th2 cells used distinct adhesion mechanisms during tumor eradication: the leukocyte function-associated antigen (LFA)-1–dependent cell–cell adhesion step was essential for Th1 cell therapy, but not for Th2 cell therapy. These findings demonstrated for the first time the distinct role of antigen-specific Th1 and Th2 cells during eradication of established tumors in vivo.
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6 September 1999
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September 06 1999
Distinct Role of Antigen-Specific T Helper Type 1 (Th1) and Th2 Cells in Tumor Eradication in Vivo
Takashi Nishimura,
Takashi Nishimura
aFrom the Section of Genetic Engineering, Research Center for Genetic Engineering and Cell Transplantation
bDepartment of Immunology, Tokai University School of Medicine, Isehara 259-1193, Japan
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Kenji Iwakabe,
Kenji Iwakabe
aFrom the Section of Genetic Engineering, Research Center for Genetic Engineering and Cell Transplantation
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Masashi Sekimoto,
Masashi Sekimoto
aFrom the Section of Genetic Engineering, Research Center for Genetic Engineering and Cell Transplantation
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Yasushi Ohmi,
Yasushi Ohmi
aFrom the Section of Genetic Engineering, Research Center for Genetic Engineering and Cell Transplantation
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Takashi Yahata,
Takashi Yahata
aFrom the Section of Genetic Engineering, Research Center for Genetic Engineering and Cell Transplantation
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Minoru Nakui,
Minoru Nakui
aFrom the Section of Genetic Engineering, Research Center for Genetic Engineering and Cell Transplantation
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Takehito Sato,
Takehito Sato
bDepartment of Immunology, Tokai University School of Medicine, Isehara 259-1193, Japan
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Sonoko Habu,
Sonoko Habu
bDepartment of Immunology, Tokai University School of Medicine, Isehara 259-1193, Japan
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Hiroyuki Tashiro,
Hiroyuki Tashiro
cBioScience Research Laboratory, Fujiya Co. Ltd., Hadano 257, Japan
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Marimo Sato,
Marimo Sato
aFrom the Section of Genetic Engineering, Research Center for Genetic Engineering and Cell Transplantation
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Akio Ohta
Akio Ohta
aFrom the Section of Genetic Engineering, Research Center for Genetic Engineering and Cell Transplantation
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Takashi Nishimura
aFrom the Section of Genetic Engineering, Research Center for Genetic Engineering and Cell Transplantation
bDepartment of Immunology, Tokai University School of Medicine, Isehara 259-1193, Japan
Kenji Iwakabe
aFrom the Section of Genetic Engineering, Research Center for Genetic Engineering and Cell Transplantation
Masashi Sekimoto
aFrom the Section of Genetic Engineering, Research Center for Genetic Engineering and Cell Transplantation
Yasushi Ohmi
aFrom the Section of Genetic Engineering, Research Center for Genetic Engineering and Cell Transplantation
Takashi Yahata
aFrom the Section of Genetic Engineering, Research Center for Genetic Engineering and Cell Transplantation
Minoru Nakui
aFrom the Section of Genetic Engineering, Research Center for Genetic Engineering and Cell Transplantation
Takehito Sato
bDepartment of Immunology, Tokai University School of Medicine, Isehara 259-1193, Japan
Sonoko Habu
bDepartment of Immunology, Tokai University School of Medicine, Isehara 259-1193, Japan
Hiroyuki Tashiro
cBioScience Research Laboratory, Fujiya Co. Ltd., Hadano 257, Japan
Marimo Sato
aFrom the Section of Genetic Engineering, Research Center for Genetic Engineering and Cell Transplantation
Akio Ohta
aFrom the Section of Genetic Engineering, Research Center for Genetic Engineering and Cell Transplantation
1used in this paper: ICAM, intercellular adhesion molecule; OVA-pep, I-Ad–binding OVA323–339 peptide; RAG, recombination activating gene; Tg, transgenic; TRA, tumor-rejection antigen
Received:
March 23 1999
Revision Requested:
June 23 1999
Accepted:
June 24 1999
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 1999 The Rockefeller University Press
1999
The Rockefeller University Press
J Exp Med (1999) 190 (5): 617–628.
Article history
Received:
March 23 1999
Revision Requested:
June 23 1999
Accepted:
June 24 1999
Citation
Takashi Nishimura, Kenji Iwakabe, Masashi Sekimoto, Yasushi Ohmi, Takashi Yahata, Minoru Nakui, Takehito Sato, Sonoko Habu, Hiroyuki Tashiro, Marimo Sato, Akio Ohta; Distinct Role of Antigen-Specific T Helper Type 1 (Th1) and Th2 Cells in Tumor Eradication in Vivo. J Exp Med 6 September 1999; 190 (5): 617–628. doi: https://doi.org/10.1084/jem.190.5.617
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