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

Item Type:Article
Title:Costimulatory signals through B7.1/CD28 prevent T cell apoptosis during target cell lysis
Creators Name:Daniel, P.T., Kroidl, A., Cayeux, S., Bargou, R.C., Blankenstein, T. and Doerken, B.
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.
Keywords:CD28 Antigens, CD80 Antigens, CD95 Antigens, Apoptosis, Breast Neoplasms, Cell Communication, Immunologic Cytotoxicity, Fas Ligand Protein, Ligands, Lymphocyte Activation, Membrane Glycoproteins, Signal Transduction, T-Lymphocyte Subsets, Cytotoxic T-Lymphocytes, Cultured Tumor Cells
Source:Journal of Immunology
Publisher:American Association of Immunologists
Page Range:3808-3815
Date:15 October 1997
Official Publication:http://www.jimmunol.org/cgi/content/abstract/159/8/3808
PubMed:View item in PubMed

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