The EBV IL-10 homologue is a selective agonist with impaired binding to the IL-10 receptor

• Published in: The Journal of immunology (1950) Vol. 158; no. 2; pp. 604 - 613
• Main Authors: Liu, Y, de Waal Malefyt, R, Briere, F, Parham, C, Bridon, JM, Banchereau, J, Moore, KW, Xu, J
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.01.1997
• Subjects: Animals; Antibodies, Monoclonal - immunology; Cells, Cultured; Epstein-Barr virus; Herpesvirus 4, Human - immunology; Herpesvirus 4, Human - metabolism; Humans; Interleukin-10; Interleukin-2 - pharmacology; Leukocytes, Mononuclear - drug effects; Mice; Protein Binding - immunology; Receptors, Interleukin - agonists; Receptors, Interleukin - drug effects; Receptors, Interleukin - metabolism; Receptors, Interleukin-10; Recombinant Proteins - pharmacology; Viral Proteins - immunology; Viral Proteins - metabolism; Viral Proteins - pharmacology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.158.2.604

BCRF1 is an EBV homologue of human IL-10 (hIL-10) and is known as viral IL-10 (vIL-10). As found earlier for the effects of vIL-10 on mouse mast cells and CD4+ T cells, the efficiency of inhibition by vIL-10 of IL-2 production by human CD4+ T cell clones is approximately 1000-fold diminished compared with hIL-10. We studied the interaction of vIL-10 and an epitope-tagged homologue, vIL-10His6, with recombinant mouse and human IL-10 receptors (mIL-10R, hIL-10R). vIL-10His6 has approximately 1000-fold lower affinity for recombinant IL-10R than does hIL-10, yet stimulates proliferation of mouse Ba/F3 (BaF)-mIL-10R- and human TF1-hIL-10R-transfected cells with a sp. act. comparable to or greater than that of the cellular cytokine. In contrast, BaF-hIL-10R cells are approximately 1000-fold less sensitive to vIL-10His6 than are BaF-mIL-10R cells. An anti-hIL-10R mAb (3F9) blocks responses to both hIL-10 and vIL-10His6, while a soluble form of hIL-10R effectively neutralizes biologic responses only to hIL-10 by both BaF-IL-10R transfectants and normal human peripheral blood cells. The results indicate that biologic responses to both hIL-10 and vIL-10 require the known IL-10R, and suggest the existence of at least one additional IL-10R subunit. We suggest that vIL-10 is a selective agonist that is impaired in its ability to bind the defined IL-10R, which we now designate as IL-10R alpha.