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B7H costimulates clonal expansion of, and cognate destruction of tumor cells by, CD8(+) T lymphocytes in vivo.

Liu X, Bai XF, Wen J, Gao JX, Liu J, Lu P, Wang Y, Zheng P, Liu Y - J. Exp. Med. (2001)

Bottom Line: 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.Taken together, our results reveal that B7H costimulates clonal expansion of, and cognate destruction by CD8(+) T lymphocytes in vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, OH 43210, USA.

ABSTRACT
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-2L(d), 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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B7–1 and/or B7–2 on host cells were required for optimal T cell division in vivo. (A) The amount of Vα8+ T cells recovered from the spleen, the percentages of the P1CTL recovered were given in the panel. (B) Distributions of CFSE intensities among the Vα8+ T cells. Naive P1CTL were labeled with CFSE and adoptively transferred into the RAG-2−/− J558-B7H tumor-bearing mice that had received either control (a mixture of rat and hamster) IgG or anti–B7–1 and B7–2 mAbs on days 0, 1, and 2 of T cell adoptive transfer. Spleen cells were harvested and analyzed on day 3 of the adoptive transfer. This experiment was repeated twice with similar results.
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fig6: B7–1 and/or B7–2 on host cells were required for optimal T cell division in vivo. (A) The amount of Vα8+ T cells recovered from the spleen, the percentages of the P1CTL recovered were given in the panel. (B) Distributions of CFSE intensities among the Vα8+ T cells. Naive P1CTL were labeled with CFSE and adoptively transferred into the RAG-2−/− J558-B7H tumor-bearing mice that had received either control (a mixture of rat and hamster) IgG or anti–B7–1 and B7–2 mAbs on days 0, 1, and 2 of T cell adoptive transfer. Spleen cells were harvested and analyzed on day 3 of the adoptive transfer. This experiment was repeated twice with similar results.

Mentions: To test if costimulation by B7–1 and B7–2 on the host APCs is required for clonal expansion of T cells, we injected anti–B7–1 and anti–B7–2 mAbs in mice that bore J558-B7H tumors and analyzed the division of T cells in the spleens. As the J558 tumor cells did not express B7–1 and B7–2, even during an ongoing immune response in vivo (31), the anti-B7 mAbs must have blocked the costimulatory function of B7–1 and B7–2 on the host APCs. As shown in Fig. 6 , anti–B7–1 and anti–B7–2 substantially reduced the division rate of T cells. Thus, despite B7H expression on the tumor cells, optimal activation of tumor-specific T cells requires costimulation by B7–1 and/or B7–2 expressed on the host APCs.


B7H costimulates clonal expansion of, and cognate destruction of tumor cells by, CD8(+) T lymphocytes in vivo.

Liu X, Bai XF, Wen J, Gao JX, Liu J, Lu P, Wang Y, Zheng P, Liu Y - J. Exp. Med. (2001)

B7–1 and/or B7–2 on host cells were required for optimal T cell division in vivo. (A) The amount of Vα8+ T cells recovered from the spleen, the percentages of the P1CTL recovered were given in the panel. (B) Distributions of CFSE intensities among the Vα8+ T cells. Naive P1CTL were labeled with CFSE and adoptively transferred into the RAG-2−/− J558-B7H tumor-bearing mice that had received either control (a mixture of rat and hamster) IgG or anti–B7–1 and B7–2 mAbs on days 0, 1, and 2 of T cell adoptive transfer. Spleen cells were harvested and analyzed on day 3 of the adoptive transfer. This experiment was repeated twice with similar results.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2195972&req=5

fig6: B7–1 and/or B7–2 on host cells were required for optimal T cell division in vivo. (A) The amount of Vα8+ T cells recovered from the spleen, the percentages of the P1CTL recovered were given in the panel. (B) Distributions of CFSE intensities among the Vα8+ T cells. Naive P1CTL were labeled with CFSE and adoptively transferred into the RAG-2−/− J558-B7H tumor-bearing mice that had received either control (a mixture of rat and hamster) IgG or anti–B7–1 and B7–2 mAbs on days 0, 1, and 2 of T cell adoptive transfer. Spleen cells were harvested and analyzed on day 3 of the adoptive transfer. This experiment was repeated twice with similar results.
Mentions: To test if costimulation by B7–1 and B7–2 on the host APCs is required for clonal expansion of T cells, we injected anti–B7–1 and anti–B7–2 mAbs in mice that bore J558-B7H tumors and analyzed the division of T cells in the spleens. As the J558 tumor cells did not express B7–1 and B7–2, even during an ongoing immune response in vivo (31), the anti-B7 mAbs must have blocked the costimulatory function of B7–1 and B7–2 on the host APCs. As shown in Fig. 6 , anti–B7–1 and anti–B7–2 substantially reduced the division rate of T cells. Thus, despite B7H expression on the tumor cells, optimal activation of tumor-specific T cells requires costimulation by B7–1 and/or B7–2 expressed on the host APCs.

Bottom Line: 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.Taken together, our results reveal that B7H costimulates clonal expansion of, and cognate destruction by CD8(+) T lymphocytes in vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, OH 43210, USA.

ABSTRACT
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-2L(d), 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.

Show MeSH
Related in: MedlinePlus