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Viral Macrophage-Inflammatory Protein-II: A Viral Chemokine That Differentially Affects Adaptive Mucosal Immunity Compared with Its Mammalian Counterparts¹

Udai P. Singh^2,*, Shailesh Singh^2,*, Palaniappan Ravichandran^*, Dennis D. Taub and James W. Lillard, Jr.^3,*

^* Department of Microbiology and Immunology, Morehouse School of Medicine, Atlanta, GA 30310; and Laboratory of Immunology, National Institute on Aging, Gerontology Research Center, Baltimore, MD 21224

Chemokines play a profound role in leukocyte trafficking and the development of adaptive immune responses. Perhaps due to their importance in host defense, viruses have adopted many of the hallmarks displayed by chemokines. In particular, viral MIP-II (vMIP-II) is a human chemokine homologue that is encoded by human herpes virus 8. vMIP-II is angiogenic, selectively chemotactic for Th2 lymphocytes, and a homologue of human I-309 and mouse TCA-3, which also differentially attracts Th2 cells. To better understand the effect of viral chemokines on mucosal immunity, we compared the affects of vMIP-II, I-309, and TCA-3 on cellular and humoral immune responses after nasal immunization with OVA. These CCR8 ligands significantly enhanced Ag-specific serum and mucosal Abs through increasing Th2 cytokine secretion by CD4⁺ T cells. These alterations in adaptive humoral and cellular responses were preceded (12 h after immunization) by an increase in CD4⁺ T and B cells in nasal tracts with decreases of these leukocyte populations in the lung. Interestingly, vMIP-II increased neutrophil infiltration in the lung and Ag-specific IL-10-secreting CD4⁺ T cells after immunization. Although I-309 increased the number of CD28-, CD40L-, and CD30-positive, Ag-stimulated naive CD4⁺ T cells, vMIP-II and TCA-3 decreased the number of CD28-, CD40L-, and CD30-positive, resting naive CD4⁺ T cells. Taken together, these studies suggest that CCR8 ligands direct host Th2 responses, and vMIP-II up-regulates IL-10 responses and limits costimulatory molecule expression to mitigate host immunity.