Inhibition of HLA‐DR Expression on Activated Human Blood Eosinophils by Transforming Growth Factor‐β1

Peripheral blood, bronchoalveolar lavage and sputum eosinophils of patients with asthma but not peripheral blood eosinophils from normal controls have been shown to express human leucocyte antigen (HLA)‐DR on their cell surface. Cytokines implicated in the activation of eosinophils, such as interleukin (IL)‐3 and granulocyte–macrophage colony‐stimulating factor (GM‐CSF), can up‐regulate HLA‐DR expression. However, little is known about antagonistic factors that might down‐regulate HLA‐DR expression on eosinophils. In this study we investigated whether transforming growth factor‐β (TGF‐β), which has been shown to reduce survival of activated eosinophils, can also modulate HLA‐DR expression on eosinophils. For this purpose, isolated peripheral blood eosinophils were stimulated with IL‐3 and GM‐CSF for 24 h and HLA‐DR expression was measured by flow cytometry. We found that while isolated eosinophils expressed low levels of surface HLA‐DR, incubation with GM‐CSF and IL‐3 increased HLA‐DR expression on eosinophils. TGF‐β alone did not change HLA‐DR expression on isolated eosinophils. However, co‐incubation of eosinophils with TGF‐β and either GM‐CSF or IL‐3 significantly decreased HLA‐DR expression compared to eosinophils incubated with either GM‐CSF or IL‐3 alone and this was not reversed by addition of IL‐5. This effect of TGF‐β on IL‐3‐induced HLA‐DR expression was attenuated dose‐dependently in the presence of monoclonal anti‐TGF‐β antibodies. Our results suggest that TGF‐β can reduce cytokine‐induced HLA‐DR expression on eosinophils and could thus influence eosinophil activation.