摘要目的 探讨耐多药(MDR)和广泛耐药(XDR)肺结核患者外周血CD3+CD16+CD56+自然杀伤(NK)T细胞、CD3-CD16+CD56+NK细胞和T细胞亚群的表达状态及其意义.方法 对2008年1月至2009年6月在上海市肺科医院住院的316例肺结核患者进行回顾性分析,其中男204例,女112例;年龄17～88岁,平均(44±16)岁;初治119例,复治197例.根据耐药情况分为MDR组146例,其中男102例,女44例,年龄19～84岁,平均(42±16)岁;XDR组77例,其中男42例,女35例,年龄18～88岁,平均(50±16)岁;敏感组93例,其中男60例,女33例,年龄17～83岁,平均(43±19)岁.另按照空洞所占肺野范围分为1～2个肺野组(132例)、3～4个肺野组(49例)和5～6个肺野组(9例).采用流式细胞仪抗体双标法检测患者外周血中NKT细胞、NK细胞和T细胞亚群表达率.两组间比较采用Wilcoxon秩和检验,多组间比较采用Kruskal-Wallis秩和检验.结果 XDR组NKT细胞和NK细胞表达率的中位数(四分位间距)[11%(6%～16%)和7%(4%～12%)]明显高于MDR组[8%(5%～14%)和6%(4%～11%)]和敏感组[7%(4%～11%)和5%(3%～9%)],3组间两两比较,差异均有统计学意义(H值分别为6.478和8.369,均P＜0.05);XDR组男性NKT细胞和NK细胞表达率[(14±9)%和(11±7)%]明显高于女性[(9±5)%和(6±4)%],CD4T细胞表达率和CD4/CD8[(38±10)%和1.9±1.3]明显低于女性[(44±10)%和2.2±0.7],两两比较,差异均有统计学意义(z值为-2.91～2.41,P＜0.05和P＜0.01);1～2个肺野组CD4 T细胞表达率最高[(42±9)%],CD8 T细胞表达率最低[(22±8)%];5～6个肺野组CD4 T细胞表达率最低[(36±11)%],CD8 T细胞表达率最高[(28±12)%],CD4/CD8最低(1.5±0.8),差异均有统计学意义(H值为8.404～16.175,均P＜0.01).结论 NKT细胞和NK细胞表达率随结核病耐药程度加重而升高,但T细胞亚群表达率不随耐药程度加重而变化.肺结核患者的空洞范围越大,其外周血中CD4T细胞和CD4/CD8值越低,CD8T细胞值越高.XDR男性肺结核患者的细胞免疫功能损害更为明显.

abstractsObjective To explore the expressions and the significance of CD3+ CD16+CD56+ NKT cells,CD3-CD16+CD56+ NK cells and T lymphocyte subsets in peripheral blood of patients with multi-drug resistant ( MDR-TB ) and extensively drug-resistant ( XDR-TB ) pulmonary tuberculosis. Methods The data of 316patients with pulmonary tuberculosis hospitalized in Shanghai Pulmonary Hospital from January 2008 to June 2009 were retrospectively analyzed, of whom 119 were newly diagnosed, and 197 were retreated patients.There were 204 males and 112 females, aged from 17 -88 years, mean ( 44 ± 16 ) years. According to the results of drug-resistance, these patients were divided into a MDR group, an XDR group and a sensitive group. There were 146 patients in the MDR group, with 102 males and 44 females, aged from 19 - 84years, mean ( 42 ± 16 ) years. There were 77 patients in the XDR group, with 42 males and 35 females,aged from 18 -88 years, mean (50 ± 16) years. There were 93 patients in the susceptible group, with 60males and 33 females, aged from 17-83 years, mean (43 ± 19) years. According to the distribution of cavitation in lung fields, these patients were also divided into 1 -2 lung field affected group (n = 132), 3 -4 lung field affected group ( n = 49 ) and 5 - 6 lung field affected group ( n = 9 ). The frequencies of NKT cells, NK cells and T cells from whole blood were tested by flow cytometry. Rank test (SAS software) was used for statistic analyses. Results The expression rate of NKT cells and NK cells was the highest in the XDR group [11%(6% - 16%) and 7% (4% - 12%)], as compared to the MDR group [8% (5% -14% ) and 6% (4% - 11% ) ], and the susceptible group [7% (4% - 11% ) and 5% (3% -9% ) ], the difference being statistically significant ( H = 6. 478 - 8. 369, P ＜ 0. 05 ). The expression rate of the NKT (14 ± 9)% and NK cells (11 ± 7)% in males of the XDR group was significantly higher than that in females [ NKT (9 ±5)% and NK cell (6 ±4)% ], while CD4(38 ± 10)% and CD4/CD8( 1.9 ± 1.3) were significantly lower than those of the females [ CD4 (44 ± 10) % and CD4/CD8 ( 2. 2 ± 0. 7 ) ], the difference being statistically significant (z = - 2. 91 - - 2. 79, P ＜ 0. 05, P ＜ 0. 01 ). The expression rate of CD4(42 ± 9)% was the highest, but CD8 (22 ± 8)% was the lowest in the 1 -2 lung field group. While in the 5-6 lung field group, the expression rate of CD4 (36 ± 11 )% was the lowest, CD8 (28 ± 12)% was the highest, and CD4/CD8 (1. 5 ±0. 8) was the lowest, the difference being statistically significant (H = 8. 404 -16. 175, P ＜0. 01 ). Conclusions With the increasing level of drug resistance, the expression rate of NKT cells and NK cells increased, while the expression of T cell subsets did not change. The value of CD4 and CD4/CD8 in peripheral blood decreased, but CD8 increased as the extent of cavitation increased in these patients. The impairment of cellular immune function in XDR-TB was more prominent in male patients.