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 solub le CD8 alpha homodimers can antagonize CD8 T cell activation in vitro, we a sked whether secretion of soluble CDS would effect cytotoxic T cell respons es in vivo. Production of soluble CD8 by a replication-defective adenovirus vector allowed persistent virus expression for up to 5 mo in C57BL/G mice and protected a second foreign transgene from rapid deletion. Soluble CD8 s electively inhibited CD8 T cell proliferation and IFN-gamma production and could also attenuate peptide-specific CD8 T cell responses in vivo. These f inding suggest that gene vector delivery of soluble CD8 may have therapeuti c applications.