重型再生障碍性贫血患者CD8+效应T细胞损伤骨髓造血途径的研究
Study on the pathways to damage hematopoiesis by CD8+ effector T cells of the patients with severe aplastic anemia
目的 研究重型再生障碍性贫血（SAA）患者外周血CD8+CD25+和CD8+HLA-DR+ T数量及其杀伤靶细胞的途径，探讨SAA的免疫发病机制。 方法 应用流式细胞术检测29例SAA（14例初治、15例缓解）患者及12名健康对照外周血CD8+CD25+和CD8+HLA-DR+ T细胞的数量及其胞浆内穿孔素、颗粒酶 B、肿瘤坏死因子-β（TNF-β）、胞膜FasL表达。 结果 SAA初治组CD8+CD25+T细胞占CD8+、CD3+T细胞的比例分别为（3.67±2.58）%和（2.25±1.35）%， 缓解组为（5.19±4.29）%和（2.98±1.35）%，正常对照组为（4.84±2.31）%和（2.11±1.88）%，三组间比较差异无统计学意义（P>0.05）。初治组CD8+HLA-DR+T细胞占CD8+T细胞比例为（39.30±8.13）%，缓解组为（20.65±5.38）%，正常对照组为（18.34±6.68）%，初治组明显高于缓解组及正常对照组（P<0.001），缓解组与正常对照组比较差异无统计学意义（P>0.05）。SAA初治组CD8+HLA-DR+T细胞占CD3+T细胞比例为（27.81±7.10）%，缓解组为（12.02±3.03）%，正常对照组为（8.50±2.33）%，初治组明显高于缓解组及正常对照组（P<0.01），缓解组明显高于正常对照组（P<0.05）。SAA初治组CD8+HLA-DR+T细胞穿孔素、颗粒酶、TNF-β、FasL中位表达比例分别为8.51%、96.08%、72.11%、94.25%，均明显高于缓解组（1.78%、85.20%、34.38%、51.20%）及正常对照组（1.86%、82.09%、17.92%、32.91%）（P<0.05），缓解组与正常对照组比较差异无统计学意义（P>0.05）。结论 SAA患者外周血CD8+HLA-DR+效应T细胞比例增多，CD8+效应T细胞杀伤靶细胞的穿孔素-颗粒酶途径、细胞因子（TNF-β）途径、Fas/FasL途径可能均参与了骨髓造血细胞损伤的过程。
Objective To investigate the quantity and their pathways to damage hematopoietic cells of CD8+CD25+ and CD8+HLA-DR+ effector T cells in peripheral blood (PB) of the patients with severe aplastic anemia(SAA) and explore the immunopathogenesis of SAA further. Methods The quantity of CD8+CD25+and CD8+HLA-DR+ cells in PB and the expressions of perforin, granzyme B, tumor necrosis factor-β(TNF -β) and FasL of 29 SAA (14 untreated and 15 recovered) patients and 12 normal controls were analyzed by flow cytometry. Results The ratio of CD8+CD25+T cells in CD8+ T cells was （3.67±2.58）% in untreated SAA patients, （5.19±4.29）% in recovered patients and （4.84±2.31）% in normal controls, and the ratios of CD8+CD25+T cells in CD3+ cells in three groups were （2.25±1.35）%, （2.98±1.35）% and （2.11±1.88）% respectively. There was no statistic difference among 3 groups（P>0.05）. The ratio of CD8+HLA-DR+T cells in CD8+T cells was （39.30±8.13）% in untreated patients, which was significantly higher than that of recovered patients[（20.65±5.38%）] and controls [（18.34±6.68%）]（P<0.001）. There was no statistic difference between recovered patients and controls（P>0.05）. CD8+HLA-DR+T cells in CD3+ cells was （27.81±7.10）% in untreated group, higher than that of recovered patients （12.02±3.03）% and controls（8.50±2.33）%（P<0.01）. And the ratio in recovered group was higher than in control group（P<0.05）. The expressions of perforin, granzyme B, TNF-β and FasL of CD8+HLA-DR+ T cells of untreated SAA patients were 8.51%、96.08%、72.11% and 94.25% respectively, higher than those of recovered patients（1.78%、85.20%、34.38%、51.20%）and controls（1.86%、82.09%、17.92%、32.91%）. There was no statistic difference between recovered patients and controls（P>0.05）. Conclusion There were elevated quantity of CD8+HLA-DR+ T cells and high expressions of perforin, granzyme B, TNF-β and FasL in SAA, which might contribute to the bone marrow failure of SAA.
邢莉民、李丽娟、吴玉红、王红蕾、王国锦、刘鸿、张田、瞿文、王珺、宋嘉、关晶、王化泉、刘春燕、付蓉、刘惠、冯乐、阮二宝、梁勇、邵宗鸿
基础医学内科学
内科学贫血，再生障碍性效应T细胞穿孔素颗粒酶BFas
internal medicineanemia aplasticeffector T cellsperforingranzyme BFas
邢莉民,李丽娟,吴玉红,王红蕾,王国锦,刘鸿,张田,瞿文,王珺,宋嘉,关晶,王化泉,刘春燕,付蓉,刘惠,冯乐,阮二宝,梁勇,邵宗鸿.重型再生障碍性贫血患者CD8+效应T细胞损伤骨髓造血途径的研究[EB/OL].(2011-03-30)[2025-08-02].http://www.paper.edu.cn/releasepaper/content/201103-1139.点此复制
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