Inhibition of T1/ST2 During Respiratory Syncytial Virus Infection Prevents T Helper Cell Type 2 (Th2)- but Not Th1-driven Immunopathology

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2001 Apr 3

PMID 11283151

Citations 49

Authors

G Walzl

S Matthews

S Kendall

J C Gutierrez-Ramos

A J Coyle

P J Openshaw

T Hussell

Affiliations

Soon will be listed here.

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.

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