Luttmann W, Franz P, Schmidt S, Barth J, Matthys H, Virchow J C
Department of Pneumology, Medical University Clinics, Freiburg, Germany.
Scand J Immunol. 1998 Dec;48(6):667-71. doi: 10.1046/j.1365-3083.1998.00446.x.
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-beta (TGF-beta), 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-beta alone did not change HLA-DR expression on isolated eosinophils. However, co-incubation of eosinophils with TGF-beta 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-beta on IL-3-induced HLA-DR expression was attenuated dose-dependently in the presence of monoclonal anti-TGF-beta antibodies. Our results suggest that TGF-beta can reduce cytokine-induced HLA-DR expression on eosinophils and could thus influence eosinophil activation.
哮喘患者的外周血、支气管肺泡灌洗物及痰液中的嗜酸性粒细胞，而非正常对照者的外周血嗜酸性粒细胞，已被证实其细胞表面可表达人类白细胞抗原（HLA）-DR。与嗜酸性粒细胞活化相关的细胞因子，如白细胞介素（IL）-3和粒细胞-巨噬细胞集落刺激因子（GM-CSF），可上调HLA-DR的表达。然而，关于可能下调嗜酸性粒细胞上HLA-DR表达的拮抗因子却知之甚少。在本研究中，我们调查了已被证明可降低活化嗜酸性粒细胞存活率的转化生长因子-β（TGF-β）是否也能调节嗜酸性粒细胞上HLA-DR的表达。为此，将分离出的外周血嗜酸性粒细胞用IL-3和GM-CSF刺激24小时，并用流式细胞术检测HLA-DR的表达。我们发现，虽然分离出的嗜酸性粒细胞表面HLA-DR表达水平较低，但与GM-CSF和IL-3共同孵育可增加嗜酸性粒细胞上HLA-DR的表达。单独的TGF-β并未改变分离出的嗜酸性粒细胞上HLA-DR的表达。然而，与单独用GM-CSF或IL-3孵育的嗜酸性粒细胞相比，嗜酸性粒细胞与TGF-β和GM-CSF或IL-3共同孵育可显著降低HLA-DR的表达，且添加IL-5并不能逆转这种作用。在单克隆抗TGF-β抗体存在的情况下，TGF-β对IL-3诱导的HLA-DR表达的这种作用呈剂量依赖性减弱。我们的结果表明，TGF-β可降低细胞因子诱导的嗜酸性粒细胞上HLA-DR的表达，从而可能影响嗜酸性粒细胞的活化。
