经早期抗逆转录病毒治疗的围生期感染 HIV 血清阴性儿童表现出 HIV 特异性 T 细胞和 B 细胞记忆的长期持久存在。
Early antiretroviral therapy-treated perinatally HIV-infected seronegative children demonstrate distinct long-term persistence of HIV-specific T-cell and B-cell memory.
机构信息
Research Unit of Congenital and Perinatal Infections, Bambino Gesù Childrens' Hospital, IRCCS.
Department of Systems Medicine, Chair of Paediatrics, University of Rome 'Tor Vergata', Rome, Italy.
出版信息
AIDS. 2020 Apr 1;34(5):669-680. doi: 10.1097/QAD.0000000000002485.
OBJECTIVE
To investigate long-term persistence of HIV-specific lymphocyte immunity in perinatally HIV-infected children treated within the first year of life.
DESIGN
Twenty perinatally HIV-infected children who received ART therapy within the first year of life (early treated) and with stable viral control (>5 years) were grouped according to their serological response to HIV.
METHODS
Western blot analysis and ELISA defined 14 HIV-seropositive and six seronegative patients. Frequencies of gp140-specific T-cell and B-cell, and T-cell cytokine production were quantified by flow cytometry in both seronegatives and seropositives. Transcriptional signatures in purified gp140-specific B-cell subsets, in response to in-vitro stimulation with HIV peptides was evaluated by multiplex RT-PCR.
RESULTS
Gp140-specific T cells and B cells persist at similar levels in both groups. A higher production of IL-21 in gp140-specific T cells was found in seropositives vs. seronegatives (P = 0.003). Gene expression in switched IgM-IgD- gp140-specific memory B cells after stimulation with HIV peptides in vitro demonstrated a differential expression of genes involved in signal transduction and activation after BCR/TLR triggering and B-cell activation. Genes relating to antibody production (PRDM1) and T-B cognate stimulation (CXCR4, IL21R) were differentially induced after in-vitro stimulation in seronegatives vs. seropositives suggesting a truncated process of B-cell maturation.
CONCLUSION
HIV-specific memory B and T cells persist in early treated regardless their serological status. Seronegatives and seropositives are distinguished by gp140-specific T-cell function and by distinct transcriptional signatures of gp140-specific B cells after in-vitro stimulation, presumably because of a different antigen exposure. Such qualitative insights may inform future immunotherapeutic interventions.
目的
研究在生命的第一年接受抗逆转录病毒治疗的围产期 HIV 感染儿童中，HIV 特异性淋巴细胞免疫的长期持久性。
设计
根据对 HIV 的血清学反应，将 20 名在生命的第一年（早期治疗）接受抗逆转录病毒治疗且病毒控制稳定（>5 年）的围产期 HIV 感染儿童分为两组。
方法
Western blot 分析和 ELISA 定义了 14 名 HIV 血清阳性和 6 名血清阴性患者。通过流式细胞术定量检测了两组血清阴性和阳性患者 gp140 特异性 T 细胞和 B 细胞以及 T 细胞细胞因子的产生。通过多重 RT-PCR 评估了在 HIV 肽体外刺激下，gp140 特异性 B 细胞亚群中纯化的转录本的特征。
结果
两组中 gp140 特异性 T 细胞和 B 细胞的水平相似。gp140 特异性 T 细胞中 IL-21 的产生在血清阳性患者中高于血清阴性患者（P=0.003）。体外用 HIV 肽刺激后，gp140 特异性记忆 B 细胞中 IgM-IgD-gp140 特异性的基因表达显示，在 BCR/TLR 触发和 B 细胞激活后，参与信号转导和激活的基因表达存在差异。与抗体产生（PRDM1）和 T-B 同源刺激（CXCR4、IL21R）相关的基因在血清阴性患者和血清阳性患者的体外刺激后差异诱导，表明 B 细胞成熟过程中断。
结论
无论其血清学状态如何，早期治疗的儿童中都存在 HIV 特异性记忆 B 和 T 细胞。血清阴性患者和血清阳性患者之间的区别在于 gp140 特异性 T 细胞的功能和体外刺激后 gp140 特异性 B 细胞的不同转录本特征，这可能是由于不同的抗原暴露。这种定性的见解可能为未来的免疫治疗干预提供信息。
Zotero 插件