Inhibition of T1/ST2 during respiratory syncytial virus infection prevents T helper cell type 2 (Th2)- but not Th1-driven immunopathology.
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.
Walzl
G
G
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.
Matthews
S
S
Kendall
S
S
Gutierrez-Ramos
J C
JC
Coyle
A J
AJ
Openshaw
P J
PJ
Hussell
T
T
D000818:Animals; D004802:Eosinophilia / Q000276:immunology / Q000628:therapy; D005260:Female; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D011506:Proteins / Q000276:immunology*; D018123:Receptors, Interleukin; D017472:Receptors, Interleukin-1 / Q000276:immunology*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000628:therapy; D006377:T-Lymphocytes, Helper-Inducer; D018417:Th1 Cells; D018418:Th2 Cells
C486189:Il1rl1 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008565:Membrane Proteins; D011506:Proteins; D018123:Receptors, Interleukin; D017472:Receptors, Interleukin-1