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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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B7H expressed on the tumor cells promotes clonal expansion of purified P1CTL. Purified CD8 T cells from P1CTL transgenic mice were labeled with CFSE and stimulated with irradiated J558-Neo or J558-B7H for either 48 or 72 h. The viable cells were stained with PE-anti-Vα8 and Cy-anti-CD8 mAbs. The data shown are histograms of gated CD8+Vα8+ T cells. This experiment was repeated twice with similar results.
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fig4: B7H expressed on the tumor cells promotes clonal expansion of purified P1CTL. Purified CD8 T cells from P1CTL transgenic mice were labeled with CFSE and stimulated with irradiated J558-Neo or J558-B7H for either 48 or 72 h. The viable cells were stained with PE-anti-Vα8 and Cy-anti-CD8 mAbs. The data shown are histograms of gated CD8+Vα8+ T cells. This experiment was repeated twice with similar results.

Mentions: We have recently produced a transgenic mouse line that expresses TCR-specific for P1A, which we called P1CTL (8). To analyze if the B7H promotes the induction of T cell clonal expansion, we labeled the purified transgenic CD8 T cells with CFSE and stimulated them with either J558-Neo or J558-B7H cells. As shown in Fig. 4 , regardless of the tumor cells used, insignificant T cell division was found at 48 h of coculture. By 72 h, however, many of the J558-B7H–stimulated T cells had mounted up to five divisions, while T cells cocultured with J558-Neo barely divided. Both groups divided at 96 h after stimulation (data not shown), although there were approximately fivefold more nondividing P1CTL in the J558-Neo stimulated culture (∼10%) than the J558-B7H–stimulated culture (∼2%). Thus, B7H accelerated T cell clonal expansion in vitro.


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)

B7H expressed on the tumor cells promotes clonal expansion of purified P1CTL. Purified CD8 T cells from P1CTL transgenic mice were labeled with CFSE and stimulated with irradiated J558-Neo or J558-B7H for either 48 or 72 h. The viable cells were stained with PE-anti-Vα8 and Cy-anti-CD8 mAbs. The data shown are histograms of gated CD8+Vα8+ T cells. This experiment was repeated twice with similar results.
© Copyright Policy
Related In: Results  -  Collection

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

fig4: B7H expressed on the tumor cells promotes clonal expansion of purified P1CTL. Purified CD8 T cells from P1CTL transgenic mice were labeled with CFSE and stimulated with irradiated J558-Neo or J558-B7H for either 48 or 72 h. The viable cells were stained with PE-anti-Vα8 and Cy-anti-CD8 mAbs. The data shown are histograms of gated CD8+Vα8+ T cells. This experiment was repeated twice with similar results.
Mentions: We have recently produced a transgenic mouse line that expresses TCR-specific for P1A, which we called P1CTL (8). To analyze if the B7H promotes the induction of T cell clonal expansion, we labeled the purified transgenic CD8 T cells with CFSE and stimulated them with either J558-Neo or J558-B7H cells. As shown in Fig. 4 , regardless of the tumor cells used, insignificant T cell division was found at 48 h of coculture. By 72 h, however, many of the J558-B7H–stimulated T cells had mounted up to five divisions, while T cells cocultured with J558-Neo barely divided. Both groups divided at 96 h after stimulation (data not shown), although there were approximately fivefold more nondividing P1CTL in the J558-Neo stimulated culture (∼10%) than the J558-B7H–stimulated culture (∼2%). Thus, B7H accelerated T cell clonal expansion in vitro.

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