急性及亚急性期布鲁菌病患者γδT等淋巴细胞的表达及其意义

The expression of γδT cells and other lymphocytes in patients with acute and subacute brucellosis and its significance

目的 观察急性及亚急性期布鲁菌病患者治疗前、后γδT细胞、CD4＋T淋巴细胞及CD8＋T淋巴细胞水平的变化及其意义.方法 2009年9月至2014年8月天津市第二人民医院收治布鲁菌病患者159例,其中急性期患者122例,亚急性期患者37例.应用流式细胞仪检测所有患者治疗前、后外周血γδT、CD4＋及CD8＋T淋巴细胞计数.并检测30名健康者作为对照组.计量资料采用￡检验及非参数Kruskal-Wallis检验.结果 布鲁菌病急性期组患者治疗前γδT细胞、CD4＋T淋巴细胞和CD8＋T淋巴细胞中位数分别为84.0/μL、780.5/μL和774.0/μL,亚急性期组分别为76.0/μL、887.0/μL和890.0/μL,健康对照组分别为49.0/μL、772.5/μL和592.5/μL.急性期组γδT细胞（U=114.5,P=0.001）和CD8＋T淋巴细胞计数（U=1 185.5,P=0.003）显著高于健康对照组,亚急性期组γδT细胞（U=359.0,P=0.013）、CD4＋T淋巴细胞（U=325.5,P=0.004）和CD8＋T淋巴细胞计数（U=316.5,P=0.003）较健康对照组显著升高,亚急性期组CD4＋T淋巴细胞显著高于急性期组（U=1 619.0,P=0.009）.完成6周治疗的急性期患者31例,亚急性期患者30例.治疗前、后急性期组γδT细胞[（120.7±104.9）/μL比（82.2±85.3）/μL;t=3.568,P=0.001]、CD4＋T淋巴细胞[（802.1±300.6）/μL比（663.0±280.6）/μL;t=2.904,P=0.007]和CD8＋T淋巴细胞[（908.1±422.7）/μL比（651.1±241.7）/μL;t=3.885,P=0.001]差异有统计学意义.治疗后亚急性期组γδT细胞[（67.1±38.4）/μL比（48.4±32.1）/μL;t=2.695,P=0.012）、CD4＋T淋巴细胞[（817.1±147.4）/μL比（650.8±196.5）/μL;t=5.301,P＜0.01）和CD8-T淋巴细胞[（703.7±191.5）/μL比（537.4±186.0）/μL;t=5.152,P＜0.01],较治疗前显著降低.结论 急性期和亚急性期布鲁菌病患者γδT细胞、CD4＋T淋巴细胞及CD8＋T淋巴细胞均发生免疫激活,激活程度与疾病进展高度相关,这有助于了解急性及亚急性期布鲁菌病患者的免疫状况.

Objective To observe the variation of the levels of γδT cells,CD4＋ and CD8＋ T lymphocytes in patients with acute and subacute brucellosis before and after treatment.Methods A total of 159 patients with brucellosis were enrolled from the Second People＆#39;s Hospital of Tianjin between September 2009 and August 2014,of which 122 were with acute phase and 37 with subacute stage.γδT cells,CD4＋ and CD8＋ T lymphocytes in peripheral blood of all patients before and after treatment were detected by flow cytometry.Thirty healthy controls were also enrolled.Measurement data were analyzed using t test and nonparametric Kruskal-Wallis test.Results The medians of γδT cells,CD4＋ and CD8＋ T lymphocyte counts of brucellosis patients with acute stage before treatment were 84.0/μL,780.5/μL and 774.0/μL,respectively,and those with subacute stage were 76.0/μL,887.0/μL and 890.0/μL,respectively.Those in control group were 49.0/μL,772.5/μL and 592.5/μL,respectively.γδT cells （U=114.5,P =0.001） and CD8＋ T lymphocyte counts （U=1 185.5,P =0.003） in acute phase group were elevated than control group.γδT cells （U=359.0,P=0.013）,CD4＋ T lymphocyte counts （U=325.5,P=0.004） and CD8＋ T lymphocyte counts （U=316.5,P=0.003） in subacute phase group were increased than control group.CD4＋ T lymphocyte counts in subacute phase group were elevated than acute phase group （U=1 619.0,P=0.009）.There were 31 patients with acute phase and 30 patients with subacute phase who completed 6-week treatment.γδT cells （[120.7 ± 104.9]/μL vs [82.2 ±85.3]/μL;t=3.568,P=0.001）,CD4＋ T lymphocyte （[802.1±300.6]/μL vs [663.0±280.6]/μL;t=2.904,P=0.007） and CD8＋ T lymphocytes counts （[908.1±422.7]/μL vs [651.1±241.7]/μL;t=3.885,P=0.001） of brucellosis patients with acute stage before and after treatment were significantly different.γδT cells （[67.1± 38.4]/μL vs [48.4±32.1]/μL;t=2.695,P=0.012）,CD4＋ T lymphocytes （[817.1± 147.4]/μL vs [650.8± 196.5]/μL;t=5.301,P〈0.01） and CD8＋ T lymphocytes counts （[703.7±191.5]/μL vs [537.4±186.0]/μL;t=5.152,P〈0.01） of brucellosis patients with subacute stage after treatment were significantly decreased compared with those of patients before treatment.Conclusions γδT cells,CD4＋ and CD8＋ T lymphocytes in patients with acute and subacute brucellosis are all in a state of immune activation.The levels of activation are highly correlated with disease progression.And detection of the variation of these cells contributes to understand the immune state of the acute and subacute brucellosis.