B7H/B7RP (hereby called B7H) is a new member of the B7 family of costimulatory molecules and interacts with inducible costimulatory molecule (ICOS). Its function for CD8 T cells has not been reported. We report here that expression of B7H on the tumor cells reduced tumorigenicity and induced immunity to subsequent challenge with parental tumor cells. The immune protection correlates with an enhanced cytotoxic T lymphocyte (CTL) response against P1A, the major tumor antigen expressed in the J558 tumor. To understand the mechanism of immune protection, we adoptively transferred transgenic T cells specific for tumor antigen P1A into mice that bore P1A-expressing tumors. We found that while the transgenic T cells divided faster in mice bearing the B7H+ tumors, optimal B7H-induced clonal expansion of P1CTL required costimulation by B7–1 and B7–2 on the endogenous host antigen-presenting cells (APCs). Interestingly, when B7H+ and B7H− tumors were coinjected, P1CTL selectively eliminated the B7H+ tumor cells. Moreover, B7H expressed on the tumor cells made them highly susceptible to destruction by CTL in vivo, even if the CTL was administrated into mice with large tumor burdens. Tumors that recurred in the P1CTL-treated mice lost transfected B7H and/or H-2Ld, the class I molecule that presents the P1A peptide. Taken together, our results reveal that B7H costimulates clonal expansion of, and cognate destruction by CD8+ T lymphocytes in vivo.
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5 November 2001
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November 05 2001
B7H Costimulates Clonal Expansion of, and Cognate Destruction of Tumor Cells by, CD8+ T Lymphocytes In Vivo
Xingluo Liu,
Xingluo Liu
Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, OH 43210
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Xue-Feng Bai,
Xue-Feng Bai
Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, OH 43210
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Jing Wen,
Jing Wen
Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, OH 43210
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Jian-Xin Gao,
Jian-Xin Gao
Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, OH 43210
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Jinqing Liu,
Jinqing Liu
Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, OH 43210
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Ping Lu,
Ping Lu
Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, OH 43210
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Yin Wang,
Yin Wang
Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, OH 43210
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Pan Zheng,
Pan Zheng
Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, OH 43210
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Yang Liu
Yang Liu
Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, OH 43210
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Xingluo Liu
Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, OH 43210
Xue-Feng Bai
Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, OH 43210
Jing Wen
Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, OH 43210
Jian-Xin Gao
Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, OH 43210
Jinqing Liu
Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, OH 43210
Ping Lu
Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, OH 43210
Yin Wang
Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, OH 43210
Pan Zheng
Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, OH 43210
Yang Liu
Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, OH 43210
Address correspondence to Yang Liu, Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, 129 Hamilton Hall, 1645 Neil Ave., Columbus, OH 43210. Phone: 614-292-3054; Fax: 614-688-8152; E-mail: [email protected]
*
Abbreviations used in this paper: GFP, green fluorescence protein; ICOS, inducible costimulatory molecule; RAG, recombination activating genes; TIL, tumor-infiltrating lymphocyte.
Received:
October 03 2000
Revision Received:
July 13 2001
Accepted:
July 24 2001
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2001
J Exp Med (2001) 194 (9): 1339–1348.
Article history
Received:
October 03 2000
Revision Received:
July 13 2001
Accepted:
July 24 2001
Citation
Xingluo Liu, Xue-Feng Bai, Jing Wen, Jian-Xin Gao, Jinqing Liu, Ping Lu, Yin Wang, Pan Zheng, Yang Liu; B7H Costimulates Clonal Expansion of, and Cognate Destruction of Tumor Cells by, CD8+ T Lymphocytes In Vivo . J Exp Med 5 November 2001; 194 (9): 1339–1348. doi: https://doi.org/10.1084/jem.194.9.1339
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