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 CD8α 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-γ 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.