外源性IL-15/IL-10受体阻断剂对HIV-1感染者T细胞体外增殖的影响  

Effect of exogenous interleukin-15 and/or interleukin-10 blockade on T lymphocytes proliferation in HIV-1-infected individuals

作　　者：李玉枝[1] 赵稳 平岖[1] 何惠达 唐漾波[1] 

机构地区：[1]广州医科大学附属广州市第八人民医院,广东广州510060 [2]广州市白云区红十字会医院,广东广州510000

出　　处：《热带医学杂志》2016年第3期275-280,292,共7页Journal of Tropical Medicine

基　　金：国家科技重大专项课题(2013ZX10004202-002-008);广州市医药卫生科技项目(20151A010121)

摘　　要：目的探讨白介素10(IL-10)受体阻断剂(Anti-IL-10R)或/和外源性IL-15(单独或联合)对HIV-1感染者T淋巴细胞增殖的影响。方法纳入50例HIV-1感染者作为研究对象,接受抗病毒治疗组(HAART组)及未接受抗病毒治疗组(HAART-na?ve组)病例分别为27例及23例。以HIV-1 P24编码区的氨基酸序列人工合成的13个肽段组成的肽段库作为特异性抗原刺激表位,采用羧乙基锗倍半氧化物(CFSE)对外周血单个核细胞(PBMC)示踪染色,在Anti-IL-10R及外源性IL-15(单独或联合)存在条件下,与PBMC共培养,流式细胞仪检测T淋巴细胞增殖情况。结果 HAART组及HAART-na?ve组,Anti-IL-10R、IL-15、Anti-IL-10R/IL-15刺激孔的CD4^+及CD8^+T的中位增殖倍数分别与对照孔比较,CD4^+T细胞的结果分别为:0.98(P=0.45),1.06(P=0.18);1.24(P=0.006),1.27(P=0.06);1.05(P=0.314),1.08(0.003),CD8^+T细胞增殖倍数分别为:0.94(P=0.45),1.17(P=0.177);1.96(P=0.000),1.37(P=0.000);1.49(P=0.000),1.34(P=0.000)。在HAART组中,CD4^+T细胞增殖与Anti-IL-10R相关(r_s=0.195,P=0.021),CD8^+T细胞增殖与IL-15相关(r_s=0.717,P<0.0001)。在HAART-na?ve组中,CD4^+及CD8^+T细胞增殖均与IL-15相关(r_s=0.341,P=0.003;r_s=0.876,P<0.0001)。无论HAART组还是HAART-na?ve组,CD4^+T细胞和CD8^+T细胞增殖与CD4、CD8、Th/Ts及HIV-1病毒载量均无明显相关性。结论外源性IL-15能促进HIV-1感染者T淋巴细胞体外增殖,并且经HAART治疗后这一作用似乎更强;IL-10R阻断剂可能对HIV-1感染者的CD4^+T淋巴细胞有潜在的体外促活化及增殖作用。Objective To investigate effects of exogenous interleukin-15 and/or interleukin-10 blockade on T lymphocytes proliferation in HIV-1-infected individuals. Methods 50 HIV-1-infected individuals were enrolled in the study. In which,27 cases were treated with highly active anti Retroviral therapy（HAART）（HAART group） and 23 cases were not treated by HAART（HAART-naive group）. Peripheral Blood Mononuclear Cells（PBMCs） from above cases of two groups were cultured by stimulation with 13 synthetic specific peptides of amino acid sequences encoding HIV-1 P24 region,in which exogenous interleukin-10 blockade（Anti-IL-10R） alone,interleukin-15（IL-15） alone,and both IL-15/Anti-IL-10 R were added respectively.2 Proliferations of T lymphocytes were assessed by using carboxyfluorescein diacetate succinimidyl ester（CFSE） labeling assay and flow cytometry. Rank-sum test and Spearman rank correlation analysis were performed. Results In HAART group and HAART-naive group,proliferations of T lymphocytes in additions of Anti-IL-10 R,IL-15,and both IL-15/Anti-IL-10 R were analyzed by comparing with controls. In the two groups,the results in CD4~＋T lymphocytes were respectively ： 0.98（P =0.45）,1.06（P =0.18）;1.24（P =0.006）,1.27（P =0.06）; 1.05（P =0.314）,1.08（0.003）; the results in CD8~＋T lymphocytes were respectively ： 0.94（P =0.45）,1.17（P =0.177）;1.96（P=0.000）,1.37（P=0.000）;1.49（P=0.000）,1.34（P=0.000）. Moreover,in HAART cases,proliferation of CD4~＋T was correlated with Anti-il-10R（r_s=0.195,P =0.021）. Proliferation of CD8~＋T was correlated with IL-15（rs=0.717,P〈 0.0001）. In HAART-naive cases,proliferation of CD4~＋T and CD8~＋T were both correlated with IL-5（r_s=0.341,P =0.003;r_s=0.876,P 〈0.0001）. In addition,proliferation of CD4~＋T and CD8~＋T showed no correlation with HIV-1 RNA,CD4~＋T and CD8~＋T lymphocytes counts,and Th/Ts ratio. Conclusions Exogenous IL-15 can promote proliferation of CD4~＋T and CD8~＋T lymphocytes in vi

关 键 词：HIV-1 IL-15 IL-10受体阻断剂 T淋巴细胞 体外增殖 

分 类 号：R512.91[医药卫生—内科学]