nav emailalert searchbtn searchbox tablepage yinyongbenwen piczone journalimg journalInfo journalinfonormal searchdiv searchzone qikanlogo popupnotification paper paperNew
2025, 06, v.38 528-533
抗逆转录病毒治疗过程中α4β7high CD4~+T细胞的动态变化及其与免疫恢复的关系
基金项目(Foundation): 新疆维吾尔自治区自然科学基金项目-面上项目(2024D01C134)
邮箱(Email): 48844066@qq.com;
DOI:
摘要:

目的 探讨人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染者接受抗逆转录病毒治疗(antiretroviral therapy,ART)过程中α4β7high CD4~+T细胞的变化特征,并揭示该细胞亚群在免疫恢复中的潜在意义。方法 选取2012—2018年在解放军总医院第五医学中心确诊并接受ART满5年的28例HIV感染者作为研究对象。分别于基线(治疗前)及治疗后1、3、5年采集外周静脉血样本,采用密度梯度离心法分离外周血单个核细胞(peripheral blood mononuclear cells,PBMCs)。运用流式细胞技术检测CD4~+T细胞绝对计数,α4β7high CD4~+T细胞绝对计数及CD4/CD8比值;同时采用荧光定量PCR技术定量检测PBMCs中HIV DNA水平。使用GraphPad Prism 8.0软件进行数据分析,组间比较采用配对t检验,相关性分析采用Pearson相关性检验。结果 在ART 0~3年期间,α4β7high CD4~+T细胞绝对计数呈现显著上升趋势(P<0.05),而在ART 3~5年保持相对稳定(P>0.05)。相关性分析显示,ART过程中α4β7high CD4~+T细胞绝对计数的动态变化与CD4~+T细胞绝对计数(r=0.890,P<0.0001)及CD4/CD8比值(r=0.408,P<0.0001)呈显著正相关,与HIV DNA水平呈负相关(r=-0.285,P=0.021)。结论 ART治疗期间患者α4β7high CD4~+T细胞的恢复可能与免疫重建密切相关。

Abstract:

Objective This study explores the characteristics of changes in α4β7high CD4~+T cells in human immunodeficiency virus(HIV) infected individuals during antiretroviral therapy(ART) and reveals the potential significance of this cell subset in immune recovery.Methods Twenty-eight HIV-infected patients who were diagnosed at the Fifth Medical Center of the PLA General Hospital and received ART for at least five years from 2012 to 2018 were selected as the research subjects.Peripheral venous blood samples were collected at baseline(before treatment) and at 1,3,and 5 years after treatment.Peripheral blood mononuclear cells(PBMCs) were isolated from the samples by density gradient centrifugation.The absolute count of CD4~+T cells,the absolute count of α4β7high CD4~+T cells and the CD4/CD8 ratio were detected by flow cytometry.At the same time,the level of HIV DNA in PBMCs was quantitatively determined by fluorescence quantitative PCR technology.Data analysis was performed using GraphPad Prism 8.0 software.Paired t-tests were used for comparisons between groups,and Pearson correlation tests were employed for correlation analysis.Results Data analysis was performed using GraphPad Prism8.0 software.Paired t-tests were used for comparisons between groups.During the ART 0-3 year period,the count of α4β7highCD4~+T cells showed a significant upward trend(P<0.05),while it remained relatively stable during the ART 3-5 year period(P>0.05).The correlation analysis revealed that the dynamic changes in the absolute count of α4β7high CD4~+T cells during the ART process were significantly positively correlated with the CD4~+T cell count(r=0.890,P<0.0001) and the CD4/CD8 ratio(r=0.408,P<0.0001),and negatively correlated with the HIV DNA level(r=-0.285,P=0.021).Conclusion During ART,the changes of α4β7high CD4~+T cell counts may play an important role in the immune recovery in HIV infected patients.

参考文献

[1]D'Angelo C,Reale M,Costantini E.Microbiota and probiotics in health and HIV infection[J].Nutrients,2017,9(6):615.DOI:10.3 3 90/nu9060615.

[2]许前磊,胡新宁,马玉青,等.从肠论治艾滋病理论探讨[J].中华中医药学刊,2022,40(7):13-15.DOI:10.13193/j.issn.1673-7717.2022.07.004.

[3]Aziz S,Fackler OT,Meyerhans A,et al.Replication of M-tropic HIV in activated human intestinal lamina propria lymphocytes is the main reason for increased virus load in the intestinal mucosa[J].J Acquir Immune Defic Syndr,2005,38(1):23-30.DOI:10.1097/00126334-200501010-00005.

[4]Schneider T,Jahn HU,Schmidt W,et al.Loss of CD4 T lymphocytes in patients infected with human immunodeficiency virus type1 is more pronounced in the duodenal mucosa than in the peripheral blood[J].Gut,1995,37(4):524-529.DOI:10.1136/gut.37.4.524.

[5]Brenchley JM,Price DA,Schacker TW,et al.Microbial translocation is a cause of systemic immune activation in chronic HIV infection[J].Nat Med,2006,12(12):1365-1371.DOI:10.1038/nm1511.

[6]Gorfu G,Rivera-Nieves J,Ley K.Role of beta7 integrins in intestinal lymphocyte homing and retention[J].Curr Mol Med,2009,9(7):836-850.DOI:10.0410/cata/6 e761b4879ac8d5748836f4d7b89b6cc.

[7]乔世峰,孙家邦,李非.整合素α4β7的表达对重症胰腺炎大鼠肠道免疫功能的调节作用[J].中国现代医学杂志,2006,5(16):689-692.DOI:1005-898(2 2006)05-0689-04.

[8]Kader M,Wang X,Piatak M,et al.Alpha4(+)beta7(hi)CD4(+)memory T cells harbor most Th-17 cells and are preferentially infected during acute SIV infection[J].Mucosal Immunol,2009,2(5):439-449.DOI:10.1038/mi.2009.90.

[9]Cicala C,Arthos J,Fauci AS.HIV envelope,integrins and co-receptor use in mucosal transmission of HIV[J].J Transl Med,2011,9(Suppl1):S2.DOI:10.1186/1479-5876-9-s1-s2.

[10]Liu Q,Lusso P.Integrin α4β7 in HIV-1 infection:a critical review[J].J Leuko Biol,2020,108(2):627-632.DOI:10.1002/JLB.4MR0120-208.

[11]Saison J,Cotte L,Chidiac C,et al.Fatal cumulative toxicities of HA ART in a stable,AIDS-free,HIV-infected patient[J].BMJ Case Rep,2012,2012:bcr1020114905.DOI:10.1136/bcr.10.2011.4905.

[12]Palella FJ Jr,Delaney KM,Moorman AC,et al.Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection[J].N Engl J Med,1998,338(13):853-860.DOI:10.1056/nejm1998032633 81301.

[13]吴雪韵,沈银忠.艾滋病抗病毒治疗新进展[J].传染病信息,2019,32(1):81-87.DOI:10.3969/j.issn.1007-8134.2019.01.019.

[14]Yang S,Arrode-Bruses G,Frank I,et al.Anti-α4β7 monoclonal an-tibody-conjugated nanoparticles block integrin α4β7 on intravaginal T cells in rhesus macaques[J].Sci Adv,2020 6(34):eabb9853.DOI:10.1126/sciadv.abb9853.

[15]Calenda G,Frank I,Arrode-Brusés G,et al.Delayed vaginal SHIV infection in VRC01 and anti-alpha4beta7 treated rhesus macaques[J].PLoS Pathog,2019,15(5):e1007776.DOI:10.1371/journal.ppat.1007776.

[16]中华医学会感染病学分会艾滋病学组,中国疾病预防控制中心,中国艾滋病诊疗指(2024版)[J].中国病毒病杂志,2025,1(15):4-32.DOI:10.16505/j.2095-0136.2025.0001.

[17]杨涛,周明菊,李华杰,等.cART治疗完全应答HIV感染者CD4/CD8比值的相关性[J].传染病信息,2019,32(2):113-118.DOI:10.3969/j.issn.1007-8134.2019.02.004.

[18]Zhang LX,Song JW,Zhang C,et al.Dynamics of HIV reservoir decay and naive CD4 T-cell recovery between immune non-responders and complete responders on long-term antiretroviral treatment[J].Clin Immunol,2021,229:108773.DOI:10.1016/j.clim.2021.108773.

[19]Brenchley JM,Douek DC.HIV infection and the gastrointestinal immune system[J].Mucosal Immunol,2008,1(1):23-30.DOI:10.103 8/mi.2007.1.

[20]Picker LJ.Immunopathogenesis of acute AIDS virus infection[J].Curr Opin Immunol,2006,18(4):399-405.DOI:10.1016/j.coi.2006.05.001.

[21]Mehandru S,Poles MA,Tenner-Racz K,et al.Primary HIV infection is associated with preferential depletion of CD4~+T lymphocytes from effector sites in the gastrointestinal tract[J].J Exp Med,2004,200(6):761-770.DOI:10.1084/j em.20041196.

[22]吴江,王蕊,计云霞,等.HIV急性期感染者肠道归巢CD4 T细胞的变化特点[J].中国艾滋病性病,2018,24(1):19-22.DOI:10.13419/j.cnki.aids.2018.01.06.

[23]李世福,高良敏,蔡英,等.未治疗HIV/AIDS中CD4+T细胞计数与机会性感染的相关性分析[J].中国皮肤性病学杂志,2017,31(3):267-272.DOI:10.13735/j.cjdv.1001-7089.201605111.

[24]陈凯,姚仕堂,王继宝,等.早发现早治疗有利于HIV感染者CD4/CD8比值的恢复[J].中国艾滋病性病,2019,25(9):891-894.DOI:10.13419/j.cnki.aids.2019.09.05.

[25]童珑,马健强,谭覃,等.艾滋病患者抗病毒治疗前后CD4/CD8比值变化及其意义[J].热带医学杂志,2016,16(7):891-893.DOI:1672-3619(2016)07-0891-03.

[26]张鹏,蒋忠胜,李敏基,等.长期抗病毒治疗的艾滋病患者CD4_CD8_比值影响因素分析[J].中国皮肤性病学杂志,2020,34(3):290-294.DOI:10.13735/j.cjdv.1001-7089.201906095.

[27]林绿,黎彦君,肖秋叶,等.HIV感染患者肠道归巢CD4~+T细胞变化与亚型的相关性[J].临床和实验医学杂志,2019,10(18):1073-1077.DOI:10.3969/j.issn.1671-4695.2019.10.019.

[28]Fadul N,Couturier J,Yu X,et al.Treatment-Naive HIV-Infected Patients Have Fewer Gut-Homing beta7 Memory CD4 T Cells than Healthy Controls[J].South Med J,2017,110(11):709-713.DOI:10.14423/smj.0000000000000730.

[29]康伟芳,蒋就喜,胡婷婷,等.整合素α4β7在肠道表达的意义[J].中国现代医学杂志,2014,8(24):55-58.DOI:1005-8982(2014)08-0055-04.

[30]Lu X,Li Z,Li Q,et al.Preferential loss of gut-homing α4β7 CD4~+T cells and their circulating functional subsets in acute HIV-1 infection[J].Cell Mol Immunol,2016,13(6):776-784.DOI:10.1038/cmi.2015.60.

[31]Uzzan M,Tokuyama M,Rosenstein AK,et al.Anti-α4β7 therapy targets lymphoid aggregates in the gastrointestinal tract of HIV-infected individuals[J].Sci Transl Med,2018,10(461):eaau4711.DOI:10.1126/scitranslmed.aau4711.

[32]Byrareddy SN,Arthos J,Cicala C,et al.Sustained virologic control in SIV+macaques after antiretroviral and α4β7 antibody therapy[J].Science,2016,354(6309):197-202.DOI:10.1126/science.aag1276.

[33]冯清法,吴宏昌,周吉坤.HIV/AIDS患者CD4/CD8细胞比值的临床价值研究进展[J].中国艾滋病性病,2025,31(2):215-220.DOI:10.13419/j.cnki.aids.2025.02.20.

[34]Besson GJ,Lalama CM,Bosch RJ,et al.HIV DNA decay dynamics in blood during more than a decade of suppressive antiretroviral therapy[J].Clin Infect Dis,2014,59(9):1312-1321.DOI:10.1093/cid/ciu585.

[35]Kimata JT,Rice AP,Wang J.Challenges and strategies for the eradication of the HIV reservoir[J].Curr Opin Immunol,2016,42:65-70.DOI:10.1016/j.coi.2016.05.015.

[36]张晴,高林,郭晓燕,等.长期ART中HIV-1抗体的水平变化特点及其与HIV-1储存库相关关系的研究[J].传染病信息,2022,35(1):46-50.DOI:10.3969/j.issn.1007-8134.2022.01.004.

基本信息:

中图分类号:R512.91

引用信息:

[1]孜来古丽·米吉提,潘珂君,马海梅,等.抗逆转录病毒治疗过程中α4β7~(high) CD4~+T细胞的动态变化及其与免疫恢复的关系[J].传染病信息,2025,38(06):528-533.

基金信息:

新疆维吾尔自治区自然科学基金项目-面上项目(2024D01C134)

发布时间:

2025-12-25

出版时间:

2025-12-25

检 索 高级检索

引用

GB/T 7714-2015 格式引文
MLA格式引文
APA格式引文