Costimulator B7-DC Attenuates Strong Th2 Responses Induced by Nippostrongylus brasiliensis

• Published in: The Journal of immunology (1950) Vol. 184; no. 4; pp. 2086 - 2094
• Main Authors: Ishiwata, Kenji, Watanabe, Naohiro, Guo, Miao, Tomihara, Kei, Brumlik, Michael J, Yagita, Hideo, Pardoll, Drew, Chen, Lieping, Shin, Tahiro
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15-02-2010
• Subjects: Animals; B7-1 Antigen - genetics; B7-1 Antigen - physiology; Cells, Cultured; Eosinophilia - immunology; Eosinophilia - parasitology; Feedback, Physiological; Immunoglobulin E - biosynthesis; Mice; Mice, Inbred BALB C; Mice, Knockout; Mice, Transgenic; Nippostrongylus - immunology; Programmed Cell Death 1 Ligand 2 Protein; Strongylida Infections - immunology; Th2 Cells - immunology; Th2 Cells - metabolism; Th2 Cells - parasitology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.0804051

The caliber and magnitude of T cell responses are regulated by costimulatory molecules following the engagement of TCRs and MHC molecules. B7-DC has the highest homology with B7-H1 in the B7 family, and both of them bind an immunoregulatory molecule, programmed death 1. Previous studies have demonstrated that B7-DC stimulates T cell proliferation and CTL generation, which sharply contrasts the inhibitory role of B7-H1. Th2 cytokines prompt B7-DC expression, which in turn enhances Th1 responses. In this study, we used an intestinal nematode, Nippostrongylus brasiliensis, to induce strong Th2 responses and to evaluate B7-DC function under Th2-polarizing conditions in vivo. By either blocking B7-DC expression during N. brasiliensis infection or by examining N. brasiliensis-infected B7-DC knockout mice, we observed enhanced eosinophilia, the overproduction of serum IgE, and increased Th2 cytokine production along with decreased Th1 cytokine production (particularly IFN-gamma production), indicating that B7-DC inhibits Th2 responses. Our results further demonstrate that the inhibition of Th2 responses by B7-DC occurs independently of programmed death 1 but conceivably acts through an as yet unknown alternative receptor that enhances Th1 responses. Although the deficiency of B7-DC expression that enhanced the production of IL-13 paradoxically resulted in better protection against N. brasiliensis infection, our results show that B7-DC plays an important role in bolstering a robust Th1 response that is required for effective antiviral and anticancer immunity, even under a strong Th2-polarizing environment induced by N. brasiliensis infection.