Local expansion of allergen-specific CD30+Th2-type gamma delta T cells in bronchial asthma.
BACKGROUND
T lymphocytes infiltrating airways during the allergic immune response play a fundamental role in recruiting other specialized cells, such as eosinophils, by secreting interleukin 5 (IL-5), and promoting local and systemic IgE synthesis by producing IL-4. Whether these presumed allergen-specific T cells are of mucosal or systemic origin is still a matter of conjecture.


METHODS
Immunophenotype, IL-4 production, and in vitro proliferative response to specific or unrelated allergens were analyzed in the bronchoalveolar lavage (BAL) fluid lymphocyte suspensions obtained from untreated patients with allergic asthma. Healthy subjects and patients affected by pulmonary sarcoidosis, a granulomatous lung disease characterized by infiltrating Th1 CD4+ lymphocytes, served as controls.


RESULTS
The proportions of gamma delta T lymphocytes, mostly CD4+ or CD4- (-)CD8-, was higher in asthmatic subjects than in controls (p < 0.05). Most BAL gamma delta CD4+ lymphocytes of asthmatic patients displayed the T cell receptor (TCR)-gamma delta V delta 1 chain. While CD30 antigen coexpression on the surface of BAL alpha beta(+) T lymphocytes was low (ranging from 5 to 12%), about half of pulmonary gamma delta T cells coexpressed it. These cells produced IL-4 and negligible amounts of interferon-gamma (IFN gamma), and proliferated in vitro in response to purified specific but not unrelated allergens. In contrast, control or sarcoidosis gamma delta T cells never displayed the CD30 surface molecule or produced significant quantities of IL-4.


CONCLUSIONS
These findings not only confirm our previous hypothesis that the allergen-specific Th2-type lymphocytes found in the lungs of asthmatic patients are gamma delta T cells belonging to airway mucosal immunocytes, but also strongly support the notion that asthma is a local rather than a systemic disease.
Spinozzi
F
F
Department of Internal Medicine, University of Perugia School of Medicine, Policlinico Monteluce, Italy.
Agea
E
E
Bistoni
O
O
Forenza
N
N
Monaco
A
A
Falini
B
B
Bassotti
G
G
De Benedictis
F
F
Grignani
F
F
Bertotto
A
A
D000328:Adult; D000485:Allergens / Q000276:immunology*; D001249:Asthma / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002469:Cell Separation; D002648:Child; D002908:Chronic Disease; D002999:Clone Cells; D016207:Cytokines / Q000032:analysis; D005434:Flow Cytometry; D006801:Humans; D017730:Ki-1 Antigen; D008168:Lung / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018418:Th2 Cells / Q000276:immunology*
D000485:Allergens; D016207:Cytokines; D017730:Ki-1 Antigen; D016692:Receptors, Antigen, T-Cell, gamma-delta