Potent immunosuppressive activities of cytomegalovirus-encoded interleukin-10.
Cytomegalovirus (CMV) has highly evolved mechanisms for avoiding detection by the host immune system. Recently, in the genomes of human and primate CMV, a novel gene comprising segments of noncontiguous open reading frames was identified and found to have limited predicted homology to endogenous cellular interleukin-10 (IL-10). Here we investigate the biological activities of the CMV IL-10-like gene product and show it to possess potent immunosuppressive properties. Both purified bacterium-derived recombinant CMV IL-10 and CMV IL-10 expressed in supernatants of human cells were found to inhibit proliferation of mitogen-stimulated peripheral blood mononuclear cells (PBMCs), with specific activity comparable to that of recombinant human IL-10. In addition, CMV IL-10 expressed from human cells inhibited cytokine synthesis, as treatment of stimulated PBMCs and monocytes with CMV IL-10 led to a marked decrease in production of proinflammatory cytokines. Finally, CMV IL-10 was observed to decrease cell surface expression of both major histocompatibility complex (MHC) class I and class II molecules, while conversely increasing expression of the nonclassical MHC allele HLA-G. These results demonstrate for the first time that CMV has a biologically active IL-10 homolog that may contribute to immune evasion during virus infection.
Spencer
Juliet V
JV
ChemoCentryx, San Carlos, California 94070, USA.
Lockridge
Kristen M
KM
Barry
Peter A
PA
Lin
Gaofeng
G
Tsang
Monica
M
Penfold
Mark E T
ME
Schall
Thomas J
TJ
D000818:Animals; D002455:Cell Division; D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000378:metabolism*; D015870:Gene Expression; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D006801:Humans; D007166:Immunosuppressive Agents; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008253:Macaca mulatta; D018123:Receptors, Interleukin / Q000378:metabolism; D053701:Receptors, Interleukin-10; D011994:Recombinant Proteins / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
C446339:CMV IL-10 protein, Cytomegalovirus; D007166:Immunosuppressive Agents; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D011994:Recombinant Proteins; D014764:Viral Proteins; D016753:Interleukin-10; D007371:Interferon-gamma