Expression cloning and characterization of a human IL-10 receptor

cDNA clones encoding a human IL-10R (hIL-10R) from a Burkitt lymphoma cell line, BJAB, express a 90 to 110 kDa polypeptide in COS7 cells that binds hIL-10 specifically. The predicted amino acid sequence of hIL-10R is 60% identical and 73% similar to mouse IL-10R (mIL-10R). rIL-10R expressed in an IL-3-dependent mouse pro-B cell line (Ba/F3) binds hIL-10 with high affinity (200 to 250 pM), and the transfected cells exhibit a proliferative response to hIL-10. Mouse IL-10 does not bind to hIL-10R, and hIL-10R-expressing Ba/F3 cells do not respond to the mouse cytokine, observations consistent with the known species specificity of IL-10. Expression of hIL-10R mRNA seems to be restricted mainly to human hemopoietic cells and cell lines. In a number of human T cell clones, expression of hIL-10R mRNA is down-regulated after activation of the cells with anti-CD3 Ab and phorbol ester. The hIL-10R gene is on human chromosome 11. Like mIL-10R, hIL-10R is structurally related to IFNR. Because IL-10 inhibits macrophage activation by IFN-gamma, this relationship suggests possible shared receptor or signal transduction pathway components.