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Abstract：
Mucosal-associated invariant T (MAIT) cell populations are reduced in frequency in HIV-1+ patients, and this disruption is associated with systemic immune activation. Reconstitution of MAIT frequency may benefit HIV-1-infected individuals; however, only recently has in vivo work been endeavored. Treatment with interleukin (IL)-2, granulocyte-macrophage colony-stimulating factor (GM-CSF), and recombinant human growth hormone (rhGH) immunotherapy combined with an HIV-1 vaccine in the context of antiretroviral therapy (ART) has shown to reconstitute CD4 T cell population numbers and function. In this study cryopreserved peripheral blood mononuclear cells (PBMCs) from 12 HIV-1+ patients who were undergoing a combination of HIV-1 vaccine and/or IL-2, GM-CSF and rhGH immunotherapy in conjunction with ART were analyzed to assess the potential of this treatment to promote MAIT cell proliferation. PBMCs were thawed from study baseline, weeks 2 and 48 time points, fluorescently stained for MAIT cell markers, and assessed by flow cytometric analysis. Matched pairs and intergroup results were statistically compared using appropriate methods. MAIT cell frequency was increased from baseline at 48 weeks in participants who received vaccine only, whereas individuals receiving IL-2, GM-CSF, and rhGH immunotherapy with or without vaccine did not show additional benefit. Although IL-2, GM-CSF, and rhGH treatment promotes CD4 T cell reconstitution and HIV-1-specific T cell function, it does not support MAIT cell recovery in patients on suppressive ART. Therapeutic immunization however has a positive effect, highlighting the importance of aiming for balanced promotion of T cell population reconstitution to impact on HIV-1 transmission and pathogenesis.
摘要：
粘膜相关的不变T（MAIT）细胞群体在HIV-1+患者中的频率降低，这种破坏与全身免疫激活有关。MAIT频率的重建可能会使HIV-1感染者受益；然而，直到最近才努力进行体内工作。白细胞介素（IL）-2，粒细胞-巨噬细胞集落刺激因子（GM-CSF），重组人生长激素（rhGH）免疫疗法与HIV-1疫苗在抗逆转录病毒疗法（ART）的背景下已显示出重建CD4T细胞群的数量和功能。在这项研究中，分析了来自12名HIV-1患者的冷冻保存的外周血单核细胞（PBMC），这些患者正在接受HIV-1疫苗和/或IL-2，GM-CSF和rhGH免疫疗法与ART的组合，以评估这种治疗促进MAIT细胞增殖的潜力。PBMC从研究基线解冻，第2周和第48周时间点，荧光染色MAIT细胞标记，并通过流式细胞仪分析进行评估。使用适当的方法对匹配对和组间结果进行统计学比较。在仅接种疫苗的参与者中，MAIT细胞频率在48周时从基线增加，而接受IL-2，GM-CSF，有或无疫苗的rhGH免疫治疗均未显示额外获益.虽然IL-2，GM-CSF，rhGH治疗促进CD4T细胞重建和HIV-1特异性T细胞功能，它不支持抑制ART患者的MAIT细胞恢复。然而，治疗性免疫具有积极的效果，强调旨在平衡促进T细胞群重建对HIV-1传播和发病机制的重要性。
