Research

CXCR3/CXCL10 interactions in the development of hypersensitivity pneumonitis

Carlo Agostini¹ , Fiorella Calabrese² , Venerino Poletti³ , Guido Marcer⁴ , Monica Facco¹ , Marta Miorin¹ , Anna Cabrelle¹ , Ilenia Baesso¹ , Renato Zambello¹ , Livio Trentin¹ and Gianpietro Semenzato¹

¹  Padua University School of Medicine, Department of Clinical and Experimental Medicine, Clinical Immunology Branch, via Giustiniani 2, 35128 Padua. Italy

²  Padua University School of Medicine, Department of Pathology, via Gabelli 61, 35121 Padua. Italy

³  G.B: Morgani Hospital, Division of Pneumology, via Forlanini 34, 47100 Forlì, Italy

⁴  Padua University School of Medicine, Department of Environmental Medicine and Public Healthy, via Giustiniani 2, 35128 Padua. Italy

author email corresponding author email

Respiratory Research 2005, 6:20doi:10.1186/1465-9921-6-20

Published:	22 February 2005

Abstract

Background

Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by repeated inhalations of finely dispersed organic particles or low molecular weight chemicals. The disease is characterized by an alveolitis sustained by CD8(+) cytotoxic T lymphocytes, granuloma formation, and, whenever antigenic exposition continues, fibrosis. Although it is known that T-cell migration into the lungs is crucial in HP reaction, mechanisms implicated in this process remain undefined.

Methods

Using flow cytometry, immunohistochemistry, confocal microscopy analysis and chemotaxis assays we evaluated whether CXCL10 and its receptor CXCR3 regulate the trafficking of CD8(+) T cells in HP lung.

Results

Our data demonstrated that lymphocytes infiltrating lung biopsies are CD8 T cells which strongly stain for CXCR3. However, T cells accumulating in the BAL of HP were CXCR3(+)/IFNγ(+) Tc1 cells exhibiting a strong in vitro migratory capability in response to CXCL10. Alveolar macrophages expressed and secreted, in response to IFN-γ, definite levels of CXCL10 capable of inducing chemotaxis of the CXCR3(+) T-cell line. Interestingly, striking levels of CXCR3 ligands could be demonstrated in the fluid component of the BAL in individuals with HP.

Conclusion

These data indicate that IFN-γ mediates the recruitment of lymphocytes into the lung via production of the chemokine CXCL10, resulting in Tc1-cell alveolitis and granuloma formation.