Human rhinoviruses inhibit the accessory function of dendritic cells by inducing sialoadhesin and B7-H1 expression

J Immunol. 2005 Jul 15;175(2):1145-52. doi: 10.4049/jimmunol.175.2.1145.

Abstract

Dendritic cells (DC) are professional APCs with an unmatched ability to interact with and activate T cells. There is accumulating evidence that DC not only efficiently stimulate T cell activation but also regulate T cell responses. However, little is known about cell surface structures on DC involved in the regulation of T cell responses. We demonstrate that human rhinoviruses (HRV) can efficiently inhibit the accessory function of DC through induction of inhibitory cell surface receptors. We observed that treatment of DC with HRV14 (R-DC), a member of the major group HRV family, diminished their T cell stimulatory capacity and induced a promiscuous and deep anergic state in cocultured T cells despite high levels of MHC molecules as well as costimulatory molecules, e.g., B7-1 (CD80) and B7-2 (CD86), and independent of inhibitory soluble factors such as IL-10. In contrast, expression of inhibitory B7-H1 molecules was up-regulated and R-DC de novo expressed sialoadhesin (Sn). Most importantly, blocking of B7-H1 and Sn on R-DC with specific mAbs against both receptors reverted the inhibitory phenotype. Thus, inhibitory signals delivered from R-DC to T cells via B7-H1 and Sn were critical for the induction of anergy. These observations suggest that an altered accessory molecule repertoire on DC upon interaction with HRV down-modulates adaptive immune responses during the viral infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Blocking / pharmacology
  • Antibodies, Monoclonal / pharmacology
  • Antigens, CD
  • B7-1 Antigen / biosynthesis*
  • B7-1 Antigen / immunology
  • B7-H1 Antigen
  • Bystander Effect / immunology
  • Cell Proliferation
  • Cells, Cultured
  • Clonal Anergy / immunology*
  • Coculture Techniques
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dendritic Cells / virology*
  • Humans
  • Lymphocyte Activation / immunology
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / biosynthesis*
  • Membrane Glycoproteins / immunology
  • Peptides / antagonists & inhibitors
  • Peptides / immunology
  • Receptors, Immunologic / antagonists & inhibitors
  • Receptors, Immunologic / biosynthesis*
  • Receptors, Immunologic / immunology
  • Rhinovirus / immunology*
  • Sialic Acid Binding Ig-like Lectin 1
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / virology*

Substances

  • Antibodies, Blocking
  • Antibodies, Monoclonal
  • Antigens, CD
  • B7-1 Antigen
  • B7-H1 Antigen
  • CD274 protein, human
  • Membrane Glycoproteins
  • Peptides
  • Receptors, Immunologic
  • SIGLEC1 protein, human
  • Sialic Acid Binding Ig-like Lectin 1