HIV-1感染者CD73~+CD8~+ T细胞减少与T细胞异常活化的相关性研究
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摘要
目的探讨HIV-1感染者外周血CD8~+T细胞上CD73的表达特点及其与T细胞异常活化和疾病进展的关系。方法研究入选65例HIV-1感染者和27例健康对照。通过流式细胞术检测研究对象外周血CD73~+CD8~+T细胞的频率和绝对计数,并将患者CD73~+CD8~+T细胞绝对计数和频率与其CD4~+T细胞计数、HIV-1载量以及CD38~+CD8~+T细胞频率进行相关性分析。结果与健康对照相比,HIV-1感染者外周血CD73~+CD8~+T细胞绝对计数和频率均明显降低(P均<0.05);HIV-1感染者外周血CD73~+CD8~+T细胞绝对计数和频率与CD4~+T细胞计数呈正相关(r=0.555,P=0.001;r=0.342,P=0.005),与CD38~+CD8~+T细胞频率呈负相关(r=-0.384,P=0.002;r=-0.387,P=0.001);HIV-1感染者CD73~+CD8~+T细胞的绝对计数与HIV-1载量呈弱负相关(r=-0.261,P=0.035)。结论 HIV-1感染者外周血CD73~+CD8~+T细胞的减少不但与患者T细胞的活化程度呈显著负相关,而且与AIDS疾病进展相关。
Objective To detect the expression of CD73 on peripheral blood CD8+ T cells in HIV-1 infected patients and analyze its correlation with disease progression and T cell abnormal activation. Methods Twenty-seven health controls and 65 HIV-1 infected patients were enrolled in this study. The frequency and absolute count of peripheral blood CD73+CD8+ T cells in all subjects were detected by flow cytometry and its correlation with CD4+ T cell counts, HIV-1 viral load and frequency of CD38+CD8+ T cells were analyzed. Results Compared with healthy controls, the absolute count and frequency of CD73+CD8+ T cells were significantly reduced in peripheral blood of HIV-1 infected patients(P <0.05); the absolute count and frequency of CD73+CD8+ T cells in peripheral blood of HIV-1 infected patients were positively correlated with CD4+ T cell counts(r=0.555, P=0.001; r=0.342, P=0.005), and negatively correlated with frequency of CD38+CD8+ T cells(r=-0.384, P=0.002; r=-0.387, P=0.001); there was a negative correlation between the absolute count of CD73+CD8+ T cells and the HIV-1 viral load in HIV-1 infected patients(r=-0.261, P=0.035). Conclusions The decrease of CD73+CD8+ T cells in HIV-1 infected patients is not only significantly negatively correlated with T cell activation, but also associated with progression of AIDS.
Objective To detect the expression of CD73 on peripheral blood CD8+ T cells in HIV-1 infected patients and analyze its correlation with disease progression and T cell abnormal activation. Methods Twenty-seven health controls and 65 HIV-1 infected patients were enrolled in this study. The frequency and absolute count of peripheral blood CD73+CD8+ T cells in all subjects were detected by flow cytometry and its correlation with CD4+ T cell counts, HIV-1 viral load and frequency of CD38+CD8+ T cells were analyzed. Results Compared with healthy controls, the absolute count and frequency of CD73+CD8+ T cells were significantly reduced in peripheral blood of HIV-1 infected patients(P <0.05); the absolute count and frequency of CD73+CD8+ T cells in peripheral blood of HIV-1 infected patients were positively correlated with CD4+ T cell counts(r=0.555, P=0.001; r=0.342, P=0.005), and negatively correlated with frequency of CD38+CD8+ T cells(r=-0.384, P=0.002; r=-0.387, P=0.001); there was a negative correlation between the absolute count of CD73+CD8+ T cells and the HIV-1 viral load in HIV-1 infected patients(r=-0.261, P=0.035). Conclusions The decrease of CD73+CD8+ T cells in HIV-1 infected patients is not only significantly negatively correlated with T cell activation, but also associated with progression of AIDS.
引文
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[24]严亚军,桂希恩,荣玉萍,等.HIV感染患者CD4+T淋巴细胞数与病毒载量分析[J].中华医院感染学杂志,2014,24(2):268-270.
[25]Appay V,Sauce D.Immune activation and inflammation in HIV-1 infection:causes and consequences[J].J Pathol,2008,214(2):231-241.
[26]李延卿,任伟宏,桑锋,等.HIV/AIDS患者免疫激活相关分子的表达及其对疾病进程的影响[J].免疫学杂志,2016,32(8):629-696.
[2]Becerra JC,Bildstein LS,Gach JS.Recent insights into the HIV/AIDS pandemic[J].Microb Cell,2016,3(9):451-475.
[3]Hileman CO,Funderburg NT.Inflammation,immune activation,and antiretroviral therapy in HIV[J].Curr HIV/AIDS Rep,2017,14(3):93-100.
[4]van Sighem A,Danner S,Ghani AC,et al.Mortality in patients with successful initial response to highly active antiretroviral therapy is still higher than in non-HIV-infected individuals[J].J Acquir Immune Defic Syndr,2005,40(2):212-218.
[5]Lohse N,Hansen AB,Pedersen G,et al.Survival of persons with and without HIV infection in Denmark,1995-2005[J].Ann Intern Med,2007,146(2):87-95.
[6]Appay V,Sauce D.Immune activation and inflammation in HIV-1 infection:causes and consequences[J].J Pathol,2008,214(2):231-241.
[7]Utay NS,Hunt PW.Role of immune activation in progression to AIDS[J].Curr Opin HIV AIDS,2016,11(2):131-137.
[8]Grund B,Neuhaus J,Phillips A.Relative risk of death in the SMART study[J].Lancet Infect Dis,2009,9(12):724-725.
[9]Liang D,Zuo A,Shao H,et al.Roles of the adenosine receptor and CD73 in the regulatory effect of gammadelta T cells[J].PLo S One,2014,9(9):e108932.
[10]Bono MR,Fernandez D,Flores-Santibanez F,et al.CD73 and CD39 ectonucleotidases in T cell differentiation:beyond immunosuppression[J].FEBS Lett,2015,589(22):3454-3460.
[11]Cekic C,Linden J.Purinergic regulation of the immune system[J].Nat Rev Immunol,2016,16(3):177-192.
[12]Linden J,Cekic C.Regulation of lymphocyte function by adenosine[J].Arterioscler Thromb Vasc Biol,2012,32(9):2097-2103.
[13]Kobie JJ,Shah PR,Yang L,et al.T regulatory and primed uncommitted CD4 T cells express CD73,which suppresses effector CD4 T cells by converting 5'-adenosine monophosphate to adenosine[J].J Immunol,2006,177(10):6780-6786.
[14]Antonioli L,Pacher P,Vizi ES,et al.CD39 and CD73 in immunity and inflammation[J].Trends Mol Med,2013,19(6):355-367.
[15]Schulze ZW J,Thomssen A,Hartjen P,et al.Comprehensive analysis of frequency and phenotype of T regulatory cells in HIV infection:CD39 expression of Fox P3+T regulatory cells correlates with progressive disease[J].J Virol,2011,85(3):1287-1297.
[16]Nikolova M,Carriere M,Jenabian MA,et al.CD39/adenosine pathway is involved in AIDS progression[J].PLo S Pathog,2011,7(7):e1002110.
[17]Moreno-Fernandez ME,Rueda CM,Rusie LK,et al.Regulatory T cells control HIV replication in activated T cells through a c AMP-dependent mechanism[J].Blood,2011,117(20):5372-5380.
[18]Toth I,Le AQ,Hartjen P,et al.Decreased frequency of CD73+CD8+T cells of HIV-infected patients correlates with immune activation and T cell exhaustion[J].J Leukoc Biol,2013,94(4):551-561.
[19]Schuler PJ,Macatangay BJ,Saze Z,et al.CD4(+)CD73(+)T cells are associated with lower T-cell activation and C reactive protein levels and are depleted in HIV-1 infection regardless of viral suppression[J].AIDS,2013,27(10):1545-1555.
[20]Carriere M,Lacabaratz C,Kok A,et al.HIV"elite controllers"are characterized by a high frequency of memory CD8+CD73+T cells involved in the antigen-specific CD8+T-cell response[J].J Infect Dis,2014,209(9):1321-1330.
[21]中华医学会感染病学分会艾滋病学组.艾滋病诊疗指南(第三版)[J].中华传染病杂志,2015,33(10):577-593.
[22]张钰,田云飞,肖江,等.有效的高效抗反转录病毒治疗后低CD4/CD8比值HIV/AIDS患者免疫学特征分析[J].传染病信息,2015,28(6):357-361.
[23]张昕,涂波,赵娟娟,等.3型天然淋巴细胞在HIV-1慢性感染中的免疫特征及其与疾病进展的关系研究[J].传染病信息,2016,29(3):144-147.
[24]严亚军,桂希恩,荣玉萍,等.HIV感染患者CD4+T淋巴细胞数与病毒载量分析[J].中华医院感染学杂志,2014,24(2):268-270.
[25]Appay V,Sauce D.Immune activation and inflammation in HIV-1 infection:causes and consequences[J].J Pathol,2008,214(2):231-241.
[26]李延卿,任伟宏,桑锋,等.HIV/AIDS患者免疫激活相关分子的表达及其对疾病进程的影响[J].免疫学杂志,2016,32(8):629-696.