Inhibition of T1/ST2 during respiratory syncytial virus infection prevents T helper cell type 2 (Th2)- but not Th1-driven immunopathology

J Exp Med. 2001 Apr 2;193(7):785-92. doi: 10.1084/jem.193.7.785.

Abstract

T cells secreting interleukin (IL)-4 and IL-5 (T helper cell type 2 [Th2] cells) play a detrimental role in a variety of diseases, but specific methods of regulating their activity remain elusive. T1/ST2 is a surface ligand of the IL-1 receptor family, expressed on Th2- but not on interferon (IFN)-gamma-producing Th1 cells. Prior exposure of BALB/c mice to the attachment (G) or fusion (F) protein of respiratory syncytial virus (RSV) increases illness severity during intranasal RSV challenge, due to Th2-driven lung eosinophilia and exuberant Th1-driven pulmonary infiltration, respectively. We used these polar models of viral illness to study the recruitment of T1/ST2 cells to the lung and to test the effects of anti-T1/ST2 treatment in vivo. T1/ST2 was present on a subset of CD4(+) cells from mice with eosinophilic lung disease. Monoclonal anti-T1/ST2 treatment reduced lung inflammation and the severity of illness in mice with Th2 (but not Th1) immunopathology. These results show that inhibition of T1/ST2 has a specific effect on virally induced Th2 responses and suggests that therapy targeted at this receptor might be of value in treating Th2-driven illness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Eosinophilia / immunology
  • Eosinophilia / therapy
  • Female
  • Interleukin-1 Receptor-Like 1 Protein
  • Membrane Proteins*
  • Mice
  • Mice, Inbred BALB C
  • Proteins / immunology*
  • Receptors, Interleukin
  • Receptors, Interleukin-1 / immunology*
  • Respiratory Syncytial Virus Infections / immunology*
  • Respiratory Syncytial Virus Infections / therapy
  • T-Lymphocytes, Helper-Inducer*
  • Th1 Cells
  • Th2 Cells

Substances

  • Il1rl1 protein, mouse
  • Interleukin-1 Receptor-Like 1 Protein
  • Membrane Proteins
  • Proteins
  • Receptors, Interleukin
  • Receptors, Interleukin-1