Costimulator B7-DC attenuates strong Th2 responses induced by Nippostrongylus brasiliensis

Kenji Ishiwata, Naohiro Watanabe, Miao Guo, Kei Tomihara, Michael J. Brumlik, Hideo Yagita, Drew Pardoll, Lieping Chen, Tahiro Shin

Research output: Contribution to journalArticlepeer-review

Abstract

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-γ 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.

Original languageEnglish (US)
Pages (from-to)2086-2094
Number of pages9
JournalJournal of Immunology
Volume184
Issue number4
DOIs
StatePublished - Feb 15 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Costimulator B7-DC attenuates strong Th2 responses induced by Nippostrongylus brasiliensis'. Together they form a unique fingerprint.

Cite this