Bratke K, Haupt F, Kuepper M, Bade B, Faehndrich S, Luttmann W, Virchow J C
Department of Pneumology, University of Rostock, Rostock, Germany.
Allergy. 2006 Nov;61(11):1351-7. doi: 10.1111/j.1398-9995.2006.01192.x.
Allergic asthma has been linked to an increase in T-helper type 2-like cytokines and T cells, but there is growing evidence for a role of lymphocyte-mediated cytotoxic mechanisms in the pathogenesis of asthma. Therefore, we investigated the cytotoxic potential of different lymphocyte subpopulations in patients with allergic asthma.
Granzyme A, B, K, and perforin expression in peripheral blood lymphocytes was analyzed using flow cytometry. Soluble granzymes were measured in serum using specific enzyme-linked immunosorbent assays.
Asthmatics had significantly decreased percentages of granzyme and perforin-positive CD4 T cells compared with non-atopic controls. In patients with asthma, the granzyme B and perforin-positive subset of CD8(+) T cells and natural killer T cells, which represent more differentiated cell populations, were significantly reduced, while this was not observed in the less differentiated granzyme K(+) subsets. In addition, the serum concentrations of granzyme B were significantly reduced in patients with asthma, while granzyme K concentrations were not different. Interestingly, there was a negative correlation between granzyme A, B and perforin expression in T cell subsets as well as serum granzyme B concentrations and total serum immunglobulin E. In CD3-negative natural killer cells, no differences in granzyme or perforin expression between patients with asthma and controls were detected.
In allergic asthma, cytotoxic T lymphocyte subsets of a more differentiated phenotype are significantly decreased and this is correlated to serum immunglobulin E levels.
过敏性哮喘与2型辅助性T细胞样细胞因子及T细胞增多有关,但越来越多的证据表明淋巴细胞介导的细胞毒性机制在哮喘发病机制中起作用。因此,我们研究了过敏性哮喘患者不同淋巴细胞亚群的细胞毒性潜能。
采用流式细胞术分析外周血淋巴细胞中颗粒酶A、B、K和穿孔素的表达。使用特异性酶联免疫吸附测定法检测血清中的可溶性颗粒酶。
与非特应性对照相比,哮喘患者颗粒酶和穿孔素阳性CD4 T细胞的百分比显著降低。在哮喘患者中,代表更分化细胞群体的CD8(+) T细胞和自然杀伤T细胞的颗粒酶B和穿孔素阳性亚群显著减少,而在分化程度较低的颗粒酶K(+)亚群中未观察到这种情况。此外,哮喘患者血清颗粒酶B浓度显著降低,而颗粒酶K浓度无差异。有趣的是,T细胞亚群中颗粒酶A、B和穿孔素的表达以及血清颗粒酶B浓度与总血清免疫球蛋白E之间存在负相关。在CD3阴性自然杀伤细胞中,未检测到哮喘患者与对照组之间颗粒酶或穿孔素表达的差异。
在过敏性哮喘中,表型更分化的细胞毒性T淋巴细胞亚群显著减少,且这与血清免疫球蛋白E水平相关。