在hiv感染无应答者中,Th2的转变和分布在Tnaϊve、TCM、TEM和TEMRA亚群中的变化

IF 3.5 3区 医学 Q3 IMMUNOLOGY
Microbial pathogenesis Pub Date : 2025-11-01 Epub Date: 2025-08-05 DOI:10.1016/j.micpath.2025.107964
Olga Loginova, Violetta Vlasova, Nadezhda Shmagel, Evgeniya Saidakova
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引用次数: 0

摘要

CD4+ t细胞计数的减少以及Th1/Th2向Th2的转变是艾滋病毒感染者在治疗前的典型特征,并与死亡风险增加有关。对接受高活性抗逆转录病毒治疗(ART)的hiv感染患者中Th2频率的研究显示了相互矛盾的结果,并且没有考虑到CD4+ t细胞计数。考虑到CD4+ t细胞恢复的效率,我们使用流式细胞术确定了抗逆转录病毒感染者中Th1 (CD4+T-bet+ ifn - γ+)和Th2 (CD4+ gada -3+IL-4+)的频率。此外,我们评估了CCR7和CD45RO的表达,以确定所研究细胞的效应潜力。我们发现,CD4+ t细胞计数< 350细胞/μL的免疫无应答者(INRs)与完全应答者(CRs)相比,Th2频率(Median (Me) =3.35%)增加,CD4+ t细胞计数< 500细胞/μL (Me=2.52%, p=0.035)和hiv阴性个体(Me=2.19%, p=0.007)。与CRs (Me=14.0 cells/μL, p=0.027)和HIV阴性个体(Me=15.8cells/μL, p=0.009)相比,INRs (Me=6.9 cells/μL)中Th2的数量有所减少,这表明不同的调控过程不仅在HIV感染的早期阶段确保了Th2的存活,而且在长期抗逆转录病毒治疗期间也确保了Th2的存活。此外,外周血CD4+、Th1和Th2细胞在Tnaϊve/TCM/TEM/TEMRA亚群中的分布也存在显著差异:CD4+ t细胞中约有一半是naïve, Th1以TEM为主,Th2以TCM为主。INRs显示初始CD4+ t细胞减少(Me=38.9%, p=0.041),而CRs Me=57.7%)和初始Th2细胞减少(Me=11.4%, p=0.049),而CRs Me=16.9%)。此外,我们注意到INRs中Th1和Th2之间的TEM细胞有轻微的扩张。相关分析显示,INRs中Th1与Th1 TEM频率呈正相关(r=0.85, p=0.003), Th2与Th2 TCM频率呈负相关(r=-0.71, p=0.027), Th1与Th1 naïve频率呈负相关(r=-0.92, p=0.0004), CD4+与CD4+TEM频率呈负相关(r=-0.66, p=0.044)。显然,INRs中的CD4+ t细胞缺乏与亚群特异性改变有关,这可能包括细胞频率和效应电位的变化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A shift towards Th2 and changes in the distribution into Tnaϊve, TCM, TEM, and TEMRA subsets in HIV-infected non-responders.

The decrease in CD4+ T-cell count, as well as a shift of Th1/Th2 towards Th2, are typical for HIV-infected people before treatment and associated with increased mortality risks. Studies of Th2 frequencies in HIV-infected patients receiving highly-active antiretroviral therapy (ART) have shown conflicting results and did not take into account CD4+ T-cell counts. We qualified the frequencies of Th1 (CD4+T-bet+IFNγ+) and Th2 (CD4+GATA-3+IL-4+) in HIV-infected individuals on ART using flow cytometry, considering the efficiency of CD4+ T-cell recovery. Additionally, we assessed the expression of CCR7 and CD45RO to determine the effector potential of the studied cells. We found that immunological non-responders (INRs), with CD4+ T-cell count <350 cells/μL, have increased frequencies of Th2 (Median (Me) = 3.35 %) compared to complete responders (CRs), with CD4+ T-cell count >500 cells/μL (Me = 2.52 %, p = 0.035) and HIV-negative individuals (Me = 2.19 %, p = 0.007). This, along with a decrease in the number of Th2 in INRs (Me = 6.9 cells/μL), compared to CRs (Me = 14.0 cells/μL, p = 0.027) and HIV-negative individuals (Me = 15.8 cells/μL, p = 0.009), indicates differential regulatory processes that ensure the Th2 survival not only in the early stages of HIV infection, but also during long-term ART. Furthermore, the distribution of peripheral blood CD4+, Th1 and Th2 cells into Tnaϊve/TCM/TEM/TEMRA subsets varied significantly: approximately half of CD4+ T-cell are naive, the majority of Th1 are TEM and the most numerous population of Th2 is TCM. INRs demonstrated a decrease in naive CD4+ T-cells (Me = 38.9 %, p = 0.041), compared to CRs Me = 57.7 %) and reduction of naive Th2 cells (Me = 11.4 %, p = 0.049), compared to CRs Me = 16.9 %). In addition, we note some minor expansion of TEM cells among Th1 and Th2 in INRs. Correlation analysis demonstrated a positive relationship between Th1 and Th1 TEM (r = 0.85, p = 0.003) frequencies, as well as negative correlations between Th2 and Th2 TCM (r = -0.71, p = 0.027), Th1 and Th1 naive (r = -0.92, p = 0.0004) and CD4+ and CD4+TEM (r = -0.66, p = 0.044) frequencies in INRs. Evidently, the CD4+ T-cell deficiency in INRs is associated with subset-specific alterations, which may include shifts in the cell frequencies and effector potential.

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来源期刊
Microbial pathogenesis
Microbial pathogenesis 医学-免疫学
CiteScore
7.40
自引率
2.60%
发文量
472
审稿时长
56 days
期刊介绍: Microbial Pathogenesis publishes original contributions and reviews about the molecular and cellular mechanisms of infectious diseases. It covers microbiology, host-pathogen interaction and immunology related to infectious agents, including bacteria, fungi, viruses and protozoa. It also accepts papers in the field of clinical microbiology, with the exception of case reports. Research Areas Include: -Pathogenesis -Virulence factors -Host susceptibility or resistance -Immune mechanisms -Identification, cloning and sequencing of relevant genes -Genetic studies -Viruses, prokaryotic organisms and protozoa -Microbiota -Systems biology related to infectious diseases -Targets for vaccine design (pre-clinical studies)
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