The alpha4 chain (CD49d), which constitutes one of the chains of alpha4beta1 (very late activating antigen-4 [VLA-4]) and alpha4beta7 integrins, mediates migration of T cells to extravascular spaces. The interaction between VLA-4 and vascular cell adhesion molecule-1 (VCAM-1) has been shown to be the critical pathway for the selective accumulation of eosinophils and basophils at sites of allergic inflammation. T lymphocytes are also specifically recruited into allergic sites, including the allergic asthmatic airway. Increased numbers of activated CD4+ cells expressing the DR antigen subset of the human leukocyte antigens (HLA-DR) appear in the allergic lung 48 h after allergen inhalation. The mechanisms by which these cells localize into the lung are still unknown. We report that stimulation of allergen-specific T cells with allergen in vitro resulted in enhanced expression of alpha4 chain (CD49d) as measured by receptor density on allergen-specific T-cell lines and T-cell clones. Kinetic studies showed that CD49d density was enhanced over a 24- to 48-h period in a time-dependent fashion, and was coordinately upregulated with HLA-DR expression. We also demonstrated that increased expression of CD49d on T-cell lines 24 h and 48 h after stimulation correlated with increased adhesion to the CS-1 fragment of fibronectin. In contrast, lymphocyte function-associated antigen-1b (LFA-1b) (CD11b), LFA-3 (CD58), and intercellular adhesion molecule-1 (ICAM-1) (CD54) expression did not change with allergen stimulation. We also showed that CD49d receptor density on T cells obtained by bronchoalveolar lavage (BAL) of allergic patients before and 48 h after allergen challenge was significantly higher than that on T cells taken from BAL of normal subjects and from controls with other inflammatory lung diseases. Taken together, these findings indicate that allergen stimulation activates allergen-specific T cells and coordinately induces increased CD49d receptor expression and binding to counterligands. We postulate that allergen-driven upregulation of CD49d, which together with the beta1 chain constitutes VLA-4 integrin, may be responsible for the selective accumulation of T cells in the allergic asthmatic lung.
CD49d expression and function on allergen-stimulated T cells from blood and airway / K.A. Pacheco, M. Tarkowski, J. Klemm, L.J. Rosenwasser. - In: AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY. - ISSN 1044-1549. - 18:2(1998 Feb), pp. 286-93-293.
|Titolo:||CD49d expression and function on allergen-stimulated T cells from blood and airway|
TARKOWSKI, MACIEJ STANISLAW (Secondo)
|Parole Chiave:||Adult; Allergens; Animals; Antigens, CD; Antigens, CD3; Bronchoalveolar Lavage Fluid; Cell Adhesion; Cell Adhesion Molecules; Cell Line; Female; Fibronectins; HLA-DR Antigens; Humans; Integrin alpha4; Integrin alpha4beta1; Integrins; Intercellular Adhesion Molecule-1; Lymphocyte Activation; Lymphocyte Subsets; Male; Mice; Peptide Fragments; Receptors, Lymphocyte Homing; Respiratory Hypersensitivity; T-Lymphocytes; Up-Regulation|
|Settore Scientifico Disciplinare:||Settore MED/10 - Malattie dell'Apparato Respiratorio|
|Data di pubblicazione:||feb-1998|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1165/ajrcmb.18.2.2687|
|Appare nelle tipologie:||01 - Articolo su periodico|