Adenosine Receptor A2a is Differentially Expressed in CD4(+) T Lymphocytes of Asthmatic and Healthy Individuals

Holopainen, P.; Karagiannidis, C.; Rückert, B.; Hense, G.; Schmidt‐Weber, C.; Blaser, K.

The endogenous nucleoside adenosine is released in excess during inflammation or other metabolic stress and is generally known to deliver tissue protective anti‐inflammatory effects. Adenosine acts via four adenosine receptors of which the A2a receptor is the predominant form in T cells. Adenosine levels are elevated in asthmatic lung, and adenosine can directly induce mast cell degranulation and bronchoconstriction in these patients. Instead, the role of anti‐inflammatory mechanisms of adenosine on T cells in asthma is unclear. Aim: To study the A2a receptor expression in peripheral blood CD4(+) T cells in asthmatic and healthy individuals using flow cytometric and quantitative real‐time PCR methods. Results: Unstimulated CD4(+) cells of asthmatic patients expressed significantly lower levels (P < 0.001) of A2a receptor in protein level (mean percentage of cells positive ± SEM: 76.8 ± 1.2, n = 6) compared to healthy individuals (90.4% ± 1.9, n = 4). Double staining for CD69 expression showed that stimulation of CD4(+) cells decreased A2a expression in both groups but indicated that the detected lower levels of A2a in unstimulated cells of asthmatics was not due to preactivation in these patients. Surprisingly, A2a mRNA expression in unstimulated CD4(+) cells was significantly higher (P < 0.05) in asthmatics (n = 28) compared to healthy controls (n = 7). The expression did not correlate with serum total IgE levels. Conclusions: Asthmatic individuals express less A2a adenosine receptor on their peripheral CD4(+) T cells. The higher mRNA levels instead may point to a negative feedback regulation in the receptor expression. The role of possibly decreased adenosine‐mediated anti‐inflammatory effects in asthma pathogenesis require further studies on this T‐cell mediated disease.