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.
AIDS. 2020 Apr 1;34(5):669-680. doi: 10.1097/QAD.0000000000002485.
To investigate long-term persistence of HIV-specific lymphocyte immunity in perinatally HIV-infected children treated within the first year of life.
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.
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.
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.
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.
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。
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。
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。
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。
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。
