CXCR3/CXCL10 interactions in the development of hypersensitivity pneumonitis.
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(+)/IFNgamma(+) Tc1 cells exhibiting a strong in vitro migratory capability in response to CXCL10. Alveolar macrophages expressed and secreted, in response to IFN-gamma, 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.


CONCLUSIONS
These data indicate that IFN-gamma mediates the recruitment of lymphocytes into the lung via production of the chemokine CXCL10, resulting in Tc1-cell alveolitis and granuloma formation.
Agostini
Carlo
C
Padua University School of Medicine, Department of Clinical and Experimental Medicine, Clinical Immunology Branch, via Giustiniani 2, 35128 Padua, Italy. carlo.agostini@unipd.it
Calabrese
Fiorella
F
Poletti
Venerino
V
Marcer
Guido
G
Facco
Monica
M
Miorin
Marta
M
Cabrelle
Anna
A
Baesso
Ilenia
I
Zambello
Renato
R
Trentin
Livio
L
Semenzato
Gianpietro
G
D000328:Adult; D000542:Alveolitis, Extrinsic Allergic / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000276:immunology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000276:immunology*
C114753:CXCL10 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D007371:Interferon-gamma
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