Abstract
T cells are central in the pathogenesis of asthma, and the associated ligand, CD40L, plays an important role by increasing production of immunoglobulin E and inflammatory mediators. β-Adrenoceptor agonists are commonly used in asthma, although little is known regarding effects on CD40L expression and T cell activation. Here, we demonstrate that cyclic adenosine monophosphate (cAMP) and β-adrenoceptor agonists differentially regulate CD40L in asthma. cAMP increased naïve T cell CD40L expression in asthmatics (9.8±8.5 increase in percent CD40L-positive cells), and expression in control subjects was inhibited (7.1±6.0 decrease in percent CD40L-positive cells; P< 0.05). Cell depletion and reconstitution experiments were used to determine that cAMP enhancement of CD40L required cell-to-cell contact with an asthma-associated natural killer (NK) cell subset. The NK cell subset expressed elevated levels of CD95, and in vitro-generated CD95+NK2 cells also produced similar effects on CD40L expression. Our findings suggest that a subset of NK cells with elevated CD95 expression is associated with asthma and can reverse cAMP inhibitory effects on T cell CD40L with the potential to increase disease exacerbation.
Original language | American English |
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Pages (from-to) | 531-541 |
Number of pages | 11 |
Journal | Journal of Leukocyte Biology |
Volume | 74 |
Issue number | 4 |
DOIs | |
State | Published - 1 Oct 2003 |
Keywords
- Allergy
- CAMP
- Cellular activation
EGS Disciplines
- Bioinformatics
- Biology
- Immunology and Infectious Disease