CD49D EXPRESSION AND FUNCTION ON ALLERGEN-STIMULATED T-CELLS FROM BLOOD AND AIRWAY

The alpha(4) chain (CD49d), which constitutes one of the chains of alp ha(4) beta(1) (very late activating antigen-4 [VLA-4]) and alpha(4) be ta(7) 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 a ccumulation of eosinophils and basophils at sites of allergic inflamma tion. T lymphocytes are also specifically recruited into allergic site s, including the allergic asthmatic airway, Increased numbers of activ ated CD4(+) cells expressing the DR antigen subset of the human leukoc yte antigens (HLA-DR) appear in the allergic lung 48 h after allergen inhalation. The mechanisms by which these cells localize into the lung an still unknown. We report that stimulation of allergen-specific T c ells with allergen in vitro resulted in enhanced expression of alpha(4 ) chain (CD49d) as measured by receptor density on allergen-specific T -cell lines and T-cell clones. Kinetic studies showed that CD49d densi ty was enhanced over a 24- to 48-h period in a time-dependent fashion, and was coordinately upregulated with HLA-DR expression. We also demo nstrated that increased expression of CD49d on T-cell lines 24 h and 4 8 h after stimulation correlated with increased adhesion to the CS-1 f ragment of fibronectin. In contrast, lymphocyte function-associated an tigen-1b (LFA-1b) (CD11b), LFA-3 (CD58), and intercellular adhesion mo lecule-1 (ICAM-1) (CD54) expression did not change with allergen stimu lation. 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 ether inflam matory lung diseases. Taken together, these findings indicate that all ergen stimulation activates allergen-specific T cells and coordinately induces increased CD49d receptor expression and binding to counterlig ands. We postulate that allergen-driven upregulation of CD49d, which t ogether with the beta(1) chain constitutes VLA-4 integrin, may be resp onsible for the selective accumulation of T cells in the allergic asth matic lung.