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Soluble CD8 attenuates cytotoxic T cell responses against replication-defective adenovirus affording transprotection of transgenes in vivo.

TitleSoluble CD8 attenuates cytotoxic T cell responses against replication-defective adenovirus affording transprotection of transgenes in vivo.
Publication TypeJournal Article
Year of Publication2000
AuthorsPeng Y, Falck-Pedersen E, Elkon KB
JournalJ Immunol
Volume165
Issue3
Pagination1470-8
Date Published2000 Aug 01
ISSN0022-1767
KeywordsAdenoviridae, Animals, CD8 Antigens, CD8-Positive T-Lymphocytes, Cytotoxicity Tests, Immunologic, Cytotoxicity, Immunologic, Defective Viruses, Epitopes, T-Lymphocyte, Gene Expression Regulation, Genetic Vectors, Immunosuppressive Agents, Injections, Intravenous, Liver, Lymphocyte Activation, Mice, Mice, Inbred BALB C, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Transgenic, Ovalbumin, Recombinant Fusion Proteins, Solubility, T-Lymphocytes, Cytotoxic, Transgenes, Virus Replication
Abstract

The T cell coreceptor, CD8, enhances T cell-APC interactions. Because soluble CD8alpha homodimers can antagonize CD8 T cell activation in vitro, we asked whether secretion of soluble CD8 would effect cytotoxic T cell responses in vivo. Production of soluble CD8 by a replication-defective adenovirus vector allowed persistent virus expression for up to 5 mo in C57BL/6 mice and protected a second foreign transgene from rapid deletion. Soluble CD8 selectively inhibited CD8 T cell proliferation and IFN-gamma production and could also attenuate peptide-specific CD8 T cell responses in vivo. These finding suggest that gene vector delivery of soluble CD8 may have therapeutic applications.

DOI10.4049/jimmunol.165.3.1470
Alternate JournalJ Immunol
PubMed ID10903752
Grant ListHL-9308-L / HL / NHLBI NIH HHS / United States

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