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

Walzl G, Matthews S, Kendall S, Gutierrez-Ramos JC, Coyle AJ, Openshaw PJ, Hussell T - J. Exp. Med. (2001)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

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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Related in: MedlinePlus

Anti-T1/ST2 treatment slows the elimination of RSV from the lungs in eosinophilic mice. Mice were scarified with Fvac (diamonds) or Gvac (squares) and challenged with RSV 14 d later. At the time points shown, lungs were removed from rat Ig–treated (closed symbols) or anti-T1/ST2–treated (open symbols) mice. Homogenized lung was assessed for the presence of RSV by plaque assay on HEp-2 cells. The results represent the mean from four individual mice.
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Figure 6: Anti-T1/ST2 treatment slows the elimination of RSV from the lungs in eosinophilic mice. Mice were scarified with Fvac (diamonds) or Gvac (squares) and challenged with RSV 14 d later. At the time points shown, lungs were removed from rat Ig–treated (closed symbols) or anti-T1/ST2–treated (open symbols) mice. Homogenized lung was assessed for the presence of RSV by plaque assay on HEp-2 cells. The results represent the mean from four individual mice.

Mentions: Prior scarification with Gvac or Fvac induces enhanced virus-specific antibody production after RSV challenge compared with mice infected with RSV alone. Anti-T1/ST2 treatment reduced this boost in antibody levels in G/RSV but not F/RSV mice (Table ). The reduction in inflammatory infiltrate and antibody titer was reflected by the delayed clearance of RSV from the lung in anti-T1/ST2–treated animals. On day 2 after RSV challenge, there was no difference in the titer of RSV recovered from the lungs of treated and untreated mice. However, G/RSV-infected mice treated with anti-T1/ST2 had reduced viral clearance at day 4 compared with untreated mice (P > 0.01), but treatment did not affect RSV clearance in F/RSV animals (P > 0.05) (Fig. 6). No virus was recovered from any group at day 7 or 10 after RSV infection.


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

Walzl G, Matthews S, Kendall S, Gutierrez-Ramos JC, Coyle AJ, Openshaw PJ, Hussell T - J. Exp. Med. (2001)

Anti-T1/ST2 treatment slows the elimination of RSV from the lungs in eosinophilic mice. Mice were scarified with Fvac (diamonds) or Gvac (squares) and challenged with RSV 14 d later. At the time points shown, lungs were removed from rat Ig–treated (closed symbols) or anti-T1/ST2–treated (open symbols) mice. Homogenized lung was assessed for the presence of RSV by plaque assay on HEp-2 cells. The results represent the mean from four individual mice.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2193366&req=5

Figure 6: Anti-T1/ST2 treatment slows the elimination of RSV from the lungs in eosinophilic mice. Mice were scarified with Fvac (diamonds) or Gvac (squares) and challenged with RSV 14 d later. At the time points shown, lungs were removed from rat Ig–treated (closed symbols) or anti-T1/ST2–treated (open symbols) mice. Homogenized lung was assessed for the presence of RSV by plaque assay on HEp-2 cells. The results represent the mean from four individual mice.
Mentions: Prior scarification with Gvac or Fvac induces enhanced virus-specific antibody production after RSV challenge compared with mice infected with RSV alone. Anti-T1/ST2 treatment reduced this boost in antibody levels in G/RSV but not F/RSV mice (Table ). The reduction in inflammatory infiltrate and antibody titer was reflected by the delayed clearance of RSV from the lung in anti-T1/ST2–treated animals. On day 2 after RSV challenge, there was no difference in the titer of RSV recovered from the lungs of treated and untreated mice. However, G/RSV-infected mice treated with anti-T1/ST2 had reduced viral clearance at day 4 compared with untreated mice (P > 0.01), but treatment did not affect RSV clearance in F/RSV animals (P > 0.05) (Fig. 6). No virus was recovered from any group at day 7 or 10 after RSV infection.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

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.

Show MeSH
Related in: MedlinePlus