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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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Expression of B7H on the tumor cells promotes T cell clonal expansion. Purified CD8 T cells from P1CTL transgenic mice were labeled with CFSE and adoptively transferred into RAG-2−/− BALB/c mice bearing either J558-Neo or J558-B7H tumors, or mice that received no tumor cells as control. At 36, 60, and 84 h after the adoptive transfer, T cells were isolated from either spleen or tumors and were analyzed for the number of divisions that they had undergone. FACS® profiles of CFSE intensity of gated CD8+Vα8+ T cells isolated from spleen were presented. The percent of the CD8+Va8+ cells were shown in the panels.
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fig5: Expression of B7H on the tumor cells promotes T cell clonal expansion. Purified CD8 T cells from P1CTL transgenic mice were labeled with CFSE and adoptively transferred into RAG-2−/− BALB/c mice bearing either J558-Neo or J558-B7H tumors, or mice that received no tumor cells as control. At 36, 60, and 84 h after the adoptive transfer, T cells were isolated from either spleen or tumors and were analyzed for the number of divisions that they had undergone. FACS® profiles of CFSE intensity of gated CD8+Vα8+ T cells isolated from spleen were presented. The percent of the CD8+Va8+ cells were shown in the panels.

Mentions: To test the function of B7H for CD8 T cell activation in vivo, we labeled P1CTL with CFSE and adoptively transferred them into syngeneic RAG-2−/− mice that were either tumor-free or bore either J558-Neo or J558-B7H tumors. At 36, 60, and 84 h after the T cell transfer, spleen cells were harvested, and the number of divisions that the transgenic T cells had undergone in vivo was analyzed by flow cytometry. As shown in Fig. 5 , left panels, P1CTL divided slowly in the tumor-free mice, with a significant number of T cell dividing only at 84 h of adoptive transfer. In the mice that bore the J558-Neo tumors, few cells divided at 36 h of transfer. By 60 h, most of the cells in the spleen were products of one to six divisions, and an overwhelming majority of the cells accumulated at 84 h were products of six or more divisions. Interestingly, the P1CTL had divided significantly faster in the mice that bore the J558-B7H tumors. Thus, significant divisions of T cells were already detected at 36 h of transfer in the J558-B7H tumor-bearing mice. By 60 h, an overwhelming majority of the T cells accumulated in the spleen had divided more than four times. Corresponding to this, substantially more T cells had accumulated in the spleen of J558-B7H tumor bearing mice at 60 and 84 h after adoptive transfer (Fig. 5).


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)

Expression of B7H on the tumor cells promotes T cell clonal expansion. Purified CD8 T cells from P1CTL transgenic mice were labeled with CFSE and adoptively transferred into RAG-2−/− BALB/c mice bearing either J558-Neo or J558-B7H tumors, or mice that received no tumor cells as control. At 36, 60, and 84 h after the adoptive transfer, T cells were isolated from either spleen or tumors and were analyzed for the number of divisions that they had undergone. FACS® profiles of CFSE intensity of gated CD8+Vα8+ T cells isolated from spleen were presented. The percent of the CD8+Va8+ cells were shown in the panels.
© Copyright Policy
Related In: Results  -  Collection

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

fig5: Expression of B7H on the tumor cells promotes T cell clonal expansion. Purified CD8 T cells from P1CTL transgenic mice were labeled with CFSE and adoptively transferred into RAG-2−/− BALB/c mice bearing either J558-Neo or J558-B7H tumors, or mice that received no tumor cells as control. At 36, 60, and 84 h after the adoptive transfer, T cells were isolated from either spleen or tumors and were analyzed for the number of divisions that they had undergone. FACS® profiles of CFSE intensity of gated CD8+Vα8+ T cells isolated from spleen were presented. The percent of the CD8+Va8+ cells were shown in the panels.
Mentions: To test the function of B7H for CD8 T cell activation in vivo, we labeled P1CTL with CFSE and adoptively transferred them into syngeneic RAG-2−/− mice that were either tumor-free or bore either J558-Neo or J558-B7H tumors. At 36, 60, and 84 h after the T cell transfer, spleen cells were harvested, and the number of divisions that the transgenic T cells had undergone in vivo was analyzed by flow cytometry. As shown in Fig. 5 , left panels, P1CTL divided slowly in the tumor-free mice, with a significant number of T cell dividing only at 84 h of adoptive transfer. In the mice that bore the J558-Neo tumors, few cells divided at 36 h of transfer. By 60 h, most of the cells in the spleen were products of one to six divisions, and an overwhelming majority of the cells accumulated at 84 h were products of six or more divisions. Interestingly, the P1CTL had divided significantly faster in the mice that bore the J558-B7H tumors. Thus, significant divisions of T cells were already detected at 36 h of transfer in the J558-B7H tumor-bearing mice. By 60 h, an overwhelming majority of the T cells accumulated in the spleen had divided more than four times. Corresponding to this, substantially more T cells had accumulated in the spleen of J558-B7H tumor bearing mice at 60 and 84 h after adoptive transfer (Fig. 5).

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