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Costimulatory signals through B7.1/CD28 prevent T cell apoptosis during target cell lysis.

P T Daniel, A Kroidl, S Cayeux, R Bargou, T Blankenstein and B Dörken
J Immunol October 15, 1997, 159 (8) 3808-3815;
P T Daniel
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A Kroidl
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S Cayeux
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R Bargou
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T Blankenstein
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B Dörken
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Abstract

Expression of B7 on tumor cells can circumvent T cell tolerance and lead to the generation of tumor cell-specific T cell immunity. The effect of B7 expression on the generation of protective antitumor immunity has been attributed primarily to 1) more efficient T cell activation and 2) better generation of tumor-specific killer T cells. We have investigated the role of costimulation through B7.1 and its receptor, the CD28 molecule, in the generation of allogeneic human CTLs against MCF-7 breast cancer cells. In this setting, we describe how activated CTLs undergo activation-induced cell death upon killing the target cell. Instead of proliferation and clonal expansion, the majority of the CTLs underwent apoptotic cell death. CTL apoptosis could be blocked by 50% when binding of the Fas ligand to its receptor, the CD95 (APO-1/Fas) molecule, was prevented. Fas ligand was detected in the activated T cells, but not in MCF-7 or a panel of other breast cancer cell lines. This excludes an active role for MCF-7 during CTL death and indicates that the CTL apoptosis is due to an autocrine production of the Fas ligand by CTLs. Costimulation of CTLs by retrovirally B7.1-transfected MCF-7 drastically reduced the sensitivity of the CTLs to apoptosis during target contact. Thus, in tumor cell vaccination, B7.1 might play a major role in preventing T cell death by altering T cell susceptibility for apoptosis.

  • Copyright © 1997 by American Association of Immunologists
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The Journal of Immunology
Vol. 159, Issue 8
15 Oct 1997
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Costimulatory signals through B7.1/CD28 prevent T cell apoptosis during target cell lysis.
P T Daniel, A Kroidl, S Cayeux, R Bargou, T Blankenstein, B Dörken
The Journal of Immunology October 15, 1997, 159 (8) 3808-3815;

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Costimulatory signals through B7.1/CD28 prevent T cell apoptosis during target cell lysis.
P T Daniel, A Kroidl, S Cayeux, R Bargou, T Blankenstein, B Dörken
The Journal of Immunology October 15, 1997, 159 (8) 3808-3815;
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Print ISSN 0022-1767        Online ISSN 1550-6606