Activated peripheral blood CD4 and CD8 T‐lymphocytes in child asthma: correlation with eosinophilia and disease severity

There now exists compelling evidence of a role for cell‐mediated immunity in the pathogenesis of adult asthma, but little information is available as to what extent this process participates in the pathogenesis of childhood asthma. We hypothesised that asthma in children is associated with the activation of T‐lymphocytes whose products regulate, at least in part, the mobilisation and recruitment of eosinophils and thereby disease severity. Our aims, therefore, were to compare the expression of activation markers, including CD45 isoforms, on peripheral blood T‐lymphocytes from asthmatic and non‐asthmatic, allergic control children matched for age and atopic status, and to attempt to correlate the percentages of activated T‐lymphocytes in the asthmatics with the numbers of peripheral blood eosinophils and with disease severity. Seventeen children with moderate to severe chronic asthma were compared with 8 non‐asthmatic, allergic children matched for age and atopic status. Expression of the activation markers CD25, HLA‐DR and VLA‐1 and the CD45 isoforms CD45RA and CD45RO on peripheral blood CD4 and CD8 T‐lymphocytes was measured using dual fluorescence flow cytometry. Peripheral blood eosinophils were measured using an automated laser cytometer. Asthma severity was assessed by a symptom score, spirometry and measurement of histamine PC20. The absolute numbers of eosinophils in the peripheral blood of the asthmatics were elevated as compared to the non‐asthmatic, allergic controls (p < 0.01), whereas the absolute numbers of both CD4+ and CD8+ T‐lymphocytes were not significantly different. The percentages and absolute numbers of CD4+ T‐lymphocytes expressing CD25 and HLA‐DR and CD8+ T‐lymphocytes expressing CD25 also were significantly elevated in the asthmatics as compared with the controls (p < 0.04 in each case). However, the percentages and absolute numbers of CD4+ T‐lymphocytes expressing VLA‐1 and CD8+ T‐lymphocytes expressing HLA‐DR and VLA‐1 did not significantly differ between the asthmatics and controls. Similarly, the percentages and absolute numbers of both CD4+ and CD8+ T‐lymphocytes expressing the CD45 isoforms CD45RA and CD45RO were not significantly different in the asthmatics and controls. In the asthmatics, the numbers of peripheral blood eosinophils correlated with disease severity as measured by histamine PC20 (p = 0.02). The percentages of CD4+ T‐lymphocytes expressing HLA‐DR correlated both with the numbers of peripheral blood eosinophils and with disease severity (histamine PC20 (p < 0.03)). In addition, the percentages of CD8+ T‐lymphocytes expressing CD25 correlated positively with disease severity as measured by a symptom and therapy score (p = 0.03). Finally, the percentages of CD8+ T‐lymphocytes expressing HLA‐DR correlated with histamine PC20 (p = 0.03). These observations are consistent with the hypothesis that activated T‐lymphocytes play a role in the pathogenesis of childhood asthma at least in part through their influence on eosinophil recruitment.