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Originally published online as doi:10.1189/jlb.0303103 on July 15, 2003

Published online before print July 15, 2003
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(Journal of Leukocyte Biology. 2003;74:531-541.)
© 2003 by Society for Leukocyte Biology

Divergence in NK cell and cyclic AMP regulation of T cell CD40L expression in asthmatic subjects

Denise Wingett*,{dagger},{ddagger},§,1 and Christopher P. Nielson*,{dagger},{ddagger}

* Research Service, Department of Veterans Affairs Medical Center, Boise, Idaho;
{dagger} Department of Medicine, Division of Gerontology and Geriatric Medicine, University of Washington, Seattle;
{ddagger} MSTI/MSMRI Research Institute of St. Luke’s Regional Medical Center, Boise, Idaho; and
§ Department of Biology, Boise State University, Boise, Idaho

1Correspondence: Boise VA Medical Center, Research Service 151, 500 W. Fort St., Boise, ID, 83702. E-mail: denise.wingett{at}med.va.gov

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. ß-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 ß-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.

Key Words: allergy • cAMP • cellular activation






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