CD4 T-LYMPHOCYTE ACTIVATION IN ASTHMA IS ACCOMPANIED BY INCREASED SERUM CONCENTRATIONS OF INTERLEUKIN-5 - EFFECT OF GLUCOCORTICOID THERAPY
CD4 T-LYMPHOCYTE ACTIVATION IN ASTHMA IS ACCOMPANIED BY INCREASED SERUM CONCENTRATIONS OF INTERLEUKIN-5 - EFFECT OF GLUCOCORTICOID THERAPY
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DOI：
10.1164/ajrccm/147.3.540
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发表时间：
1993-03-01
期刊：
影响因子：
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通讯作者：
KAY, AB
中科院分区：
文献类型：
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作者：
CORRIGAN, CJ;HACZKU, A;KAY, AB
外周血单个核细胞（PBMC）和血清，在两个场合，从15个哮喘患者谁需要口服糖皮质激素治疗中度至重度疾病恶化。在口服糖皮质激素开始前即刻（第1天）和治疗7天后（第7天）肺功能显著改善时再次采集样本。还从一组7名未接受治疗的志愿者中分离了两次样本，间隔7天。流式细胞术检测CD 4和CD 8 T淋巴细胞表面CD 25、人类淋巴细胞抗原（HLA-）DR、CD 45 RA和CD 45 RO的表达，酶联免疫吸附试验检测血清白细胞介素-5（IL-5）浓度。在第1天，与对照受试者相比，哮喘患者显示出表达标志物CD 25、HLA-DR和CD 45 RO的CD 4 T淋巴细胞的百分比显著更高，而表达CD 45 RA的CD 4 T细胞的百分比显著更低。在糖皮质激素治疗后，哮喘患者中表达CD 25、HLA-DR和CD 45 RO的CD 4 T细胞的百分比显著降低，表达CD 45 RA的百分比显著增加，因此到第7天，所有四种标志物的表达与对照受试者不再有显著差异。相比之下，第1天哮喘患者PBMC中表达HLA-DR、CD 45 RA和CD 45 RO的CD 8 T细胞的百分比与对照受试者中的那些没有显著差异，而表达CD 25的CD 8 T细胞的百分比仅略微升高。糖皮质激素治疗导致CD T细胞上所有四种标志物的表达无显著变化。IL-5在第1天的8名哮喘患者（外周血嗜酸性粒细胞计数最高的患者）的血清中可检测到，但在糖皮质激素治疗后的第7天，这些患者中无一人可检测到。治疗还与外周血嗜酸性粒细胞计数显著下降相关。在两种情况下，所有对照受试者的血清IL-5均检测不到。这些观察结果与以下假设一致：哮喘恶化与分泌IL-5的“记忆"CD 4 T淋巴细胞的激活有关，IL-5调节嗜酸性粒细胞增多，糖皮质激素治疗导致这些细胞的激活状态降低，同时抑制IL-5分泌。
Peripheral blood mononuclear cells (PBMC) and serum were obtained, on two occasions, from 15 asthmatic patients who required oral glucocorticoid therapy for moderate to severe disease exacerbations. Samples were obtained immediately before commencement of oral glucocorticoids (Day 1) and again after 7 days of treatment (Day 7), when lung function had significantly improved. Samples were also isolated on two occasions 7 days apart from a group of seven untreated volunteers. Expression of CD25, human lymphocyte antigen (HLA-)DR, CD45RA, and CD45RO on CD4 and CD8 T lymphocytes was measured by flow cytometry, and serum concentrations of interleukin-5 (IL-5) were measured using an enzyme-linked immunosorbent assay technique. On Day 1 the asthmatic patients showed significantly higher percentages, as compared with the control subjects of CD4 T lymphocytes expressing the markers CD25, HLA-DR, and CD45RO and significantly lower percentages of CD4 T cells expressing CD45RA. After glucocorticoid therapy, the percentages of CD4 T cells expressing CD25, HLA-DR, and CD45RO were significantly reduced in the asthmatic patients, and the percentages of those expressing CD45RA significantly increased so that by Day 7 expression of all four markers was no longer significantly different from that of the control subjects. By contrast, the percentages of CD8 T cells expressing HLA-DR, CD45RA, and CD45RO in the PBMC of the asthmatic patients on Day 1 were not significantly different from those in control subjects, whereas the percentages of CD25 expressing CD8 T cells were only marginally elevated. Glucocorticoid therapy resulted in no significant change in the expression of all four markers on CD T cells. IL-5 was detectable in the serum of eight of the asthmatic patients on Day 1 (those with the highest peripheral blood eosinophil counts) but in none of these patients on Day 7 after glucocorticoid therapy. Therapy was also associated with a significant fall in the peripheral blood eosinophil counts. Serum IL-5 was undetectable in all the control subjects on both occasions. These observations are consistent with the hypotheses that exacerbations of asthma are associated with activation of ''memory'' CD4 T lymphocytes secreting IL-5, which regulates eosinophilia, and that glucocorticoid therapy results in reduction of the activation status of these cells concomitant with inhibition of IL-5 secretion.