Soluble CD8 attenuates cytotoxic T cell responses against replication-defective adenovirus affording transprotection of transgenes in vivo.
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.
Peng
Y
Y
Departments ofMedicine and Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA.
Falck-Pedersen
E
E
Elkon
K B
KB
D000256:Adenoviridae / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D000818:Animals; D016827:CD8 Antigens / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003673:Defective Viruses / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology; D007166:Immunosuppressive Agents / Q000097:blood / Q000494:pharmacology; D007275:Injections, Intravenous; D008099:Liver / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012995:Solubility; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology; D019076:Transgenes / Q000276:immunology*; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
D016827:CD8 Antigens; D018984:Epitopes, T-Lymphocyte; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D010047:Ovalbumin