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

doi:10.1084/jem.193.7.785

Published online 26 March 2001.

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© The Rockefeller University Press, 0022-1007/2001/4/785/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 7, April 2, 2001 785-792

Original Article

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

Gerhard Walzl^a, Stephen Matthews^a, Sharon Kendall^a, Jose Carlos Gutierrez-Ramos^b, Anthony J. Coyle^b, Peter J.M. Openshaw^a, and Tracy Hussell^a
^a Department of Respiratory Medicine, National Heart and Lung Institute at St. Mary's Hospital, Imperial College of Science, Technology and Medicine, London W2 1PG, United Kingdom
^b Department of Biology, Inflammation Division, Millennium Pharmaceuticals, Incorporated, Cambridge, Massachusetts 02139

Correspondence to: Peter J.M. Openshaw, Department of Respiratory Medicine, National Heart and Lung Institute at St. Mary's, Imperial College School of Medicine, Norfolk Place, London W2 1PG, UK. Tel:44-0-20-7-594-3853 Fax:44-0-20-7-262-8913 E-mail:p.openshaw{at}ic.ac.uk.

T cells secreting interleukin (IL)-4 and IL-5 (T helper celltype 2 [Th2] cells) play a detrimental role in a variety ofdiseases, but specific methods of regulating their activityremain elusive. T1/ST2 is a surface ligand of the IL-1 receptorfamily, expressed on Th2- but not on interferon (IFN)- ${gamma}$ –producingTh1 cells. Prior exposure of BALB/c mice to the attachment (G)or fusion (F) protein of respiratory syncytial virus (RSV) increasesillness severity during intranasal RSV challenge, due to Th2-drivenlung eosinophilia and exuberant Th1-driven pulmonary infiltration,respectively. We used these polar models of viral illness tostudy the recruitment of T1/ST2 cells to the lung and to testthe effects of anti-T1/ST2 treatment in vivo. T1/ST2 was presenton a subset of CD4⁺ cells from mice with eosinophilic lung disease.Monoclonal anti-T1/ST2 treatment reduced lung inflammation andthe severity of illness in mice with Th2 (but not Th1) immunopathology.These results show that inhibition of T1/ST2 has a specificeffect on virally induced Th2 responses and suggests that therapytargeted at this receptor might be of value in treating Th2-drivenillness.

Key Words: bronchiolitis, viral, immunity, mucosal, immunity, cellular,pulmonary infection, eosinophil

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