Enhanced expression of fas ligand (CD95L) on T cells after segmental allergen provocation in asthma.

Abstract

Little is known about the termination of the T-cell driven inflammation found in patients with allergic asthma. Because signals delivered through Fas/Fas ligand can lead to T-cell apoptosis, we investigated the expression of Fas and Fas ligand on peripheral blood- and bronchoalveolar lavage fluid (BALF)-derived T cells and the percentage of apoptotic BALF cells in asthma. Nine atopic subjects with mild asthma and 9 control subjects underwent segmental sham and allergen challenge. Flow cytometry was used to determine the T-cell expression of Fas and Fas ligand, and the terminal dUTP nick end labeled technique was applied to detect apoptotic BALF cells. In asthmatic and control subjects almost all T cells in the BALF expressed Fas antigen without changes after saline or allergen challenge. A small percentage of T cells in BALF expressed the Fas ligand. In asthmatic subjects, but not in control subjects, there was a significant increase in Fas ligand after allergen challenge (CD3: 0.8% +/- 0.6% [baseline] vs 3.2% +/- 1.2% [allergen challenge]; CD4: 1.8% +/- 0.0% vs 4.3% +/- 1.8%; CD8: 2.8% +/- 2.4% vs 9.1% +/- 4.8%) but not after saline challenge, with a significant correlation to the percentage of BALF eosinophils. Apoptotic BALF cells were localized exclusively in macrophages at a very low frequency (0.03% to 0.15%) and without changes after saline or allergen challenge in both groups. In asthma there is an upregulation of Fas ligand on T cells in BALF after allergen challenge. Because there is no evidence for increased apoptosis, this phenomenon may reflect antigen-induced T-cell activation rather than apoptosis.