Role of Early Life Cytotoxic T Lymphocyte and Natural Killer Cell Immunity in Paediatric HIV Cure/Remission in the Anti-Retroviral Therapy Era.
Role of Early Life Cytotoxic T Lymphocyte and Natural Killer Cell Immunity in Paediatric HIV Cure/Remission in the Anti-Retroviral Therapy Era.
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早期生命的细胞毒性T淋巴细胞和天然杀伤细胞免疫在抗逆转录病毒疗法时期的儿科HIV治疗/缓解中的作用。
DOI：
10.3389/fimmu.2022.886562
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
过去十年中，仅描述了三起儿童艾滋病毒感染的功能性治愈病例。这强调了这样一个事实：早期开始联合抗逆转录病毒疗法（cART）虽然可以最大限度地减少病毒库的大小，但不足以实现治愈，除非有其他因素的影响。在本次综述中，我们考虑了这些可能促进儿科感染功能性治愈的其他因素。在生命早期的免疫活动中，包括 HIV 特异性细胞毒性 T 淋巴细胞 (CTL) 和自然杀伤 (NK) 细胞反应。与成人感染相比，前者在儿童中的抗病毒功效较差，而且事实上，在生命早期，NK 反应在抑制病毒复制方面比 CTL 具有更大的影响。与成人感染相比，这一事实可能有助于实现儿童感染功能性治愈的更大潜力，因为成人的治疗后控制与高效 CTL 活性的相关性较小，而与有效的抗病毒 NK 细胞反应的相关性更大。尽管如此，抗病毒 CTL 反应在整个童年时期可以发挥越来越有效的作用，特别是在表达“保护性”HLA-I 分子 HLA-B*27/57/58:01/8101 的个体中。讨论了先天系统在预防感染、塑造传播的特定病毒以及影响结果方面的作用。女性胎儿对子宫内母婴传播的易感性，特别是在最近产妇感染的情况下，这是一个令人好奇的问题，这也为实现治愈的机制提供了线索，因为初步发现，在中断 cART 的男性中，病毒反弹的频率较低。讨论了广泛中和抗体疗法促进接受早期 cART 儿童治愈的潜力。最后，我们提请注意儿童艾滋病毒流行状况的变化对治愈潜力的影响。 cART 的作用不仅限于预防艾滋病和降低传播风险。 cART 也会影响哪些母亲会传播病毒。母亲不再会传播那些携带与艾滋病毒免疫控制不良相关的基因的母亲。在 cART 时代，传播母亲中很大一部分（在我们的南非研究中超过 70%）是在怀孕期间发生血清转化或由于社会原因在怀孕后期被诊断出来的母亲。因此，现在，将艾滋病毒传染给孩子的母亲体内，与艾滋病毒免疫控制不良相关的基因并没有丰富。这些变化可能会影响 HLA 相关免疫反应的有效性，从而影响儿童的治愈潜力。
Only three well-characterised cases of functional cure have been described in paediatric HIV infection over the past decade. This underlines the fact that early initiation of combination antiretroviral therapy (cART), whilst minimising the size of the viral reservoir, is insufficient to achieve cure, unless other factors contribute. In this review, we consider these additional factors that may facilitate functional cure in paediatric infection. Among the early life immune activity, these include HIV-specific cytotoxic T-lymphocyte (CTL) and natural killer (NK) cell responses. The former have less potent antiviral efficacy in paediatric compared with adult infection, and indeed, in early life, NK responses have greater impact in suppressing viral replication than CTL. This fact may contribute to a greater potential for functional cure to be achieved in paediatric versus adult infection, since post-treatment control in adults is associated less with highly potent CTL activity, and more with effective antiviral NK cell responses. Nonetheless, antiviral CTL responses can play an increasingly effective role through childhood, especially in individuals expressing then ‘protective’ HLA-I molecules HLA-B*27/57/58:01/8101. The role of the innate system on preventing infection, in shaping the particular viruses transmitted, and influencing outcome is discussed. The susceptibility of female fetuses to in utero mother-to-child transmission, especially in the setting of recent maternal infection, is a curiosity that also provides clues to mechanisms by which cure may be achieved, since initial findings are that viral rebound is less frequent among males who interrupt cART. The potential of broadly neutralising antibody therapy to facilitate cure in children who have received early cART is discussed. Finally, we draw attention to the impact of the changing face of the paediatric HIV epidemic on cure potential. The effect of cART is not limited to preventing AIDS and reducing the risk of transmission. cART also affects which mothers transmit. No longer are mothers who transmit those who carry genes associated with poor immune control of HIV. In the cART era, a high proportion (>70% in our South African study) of transmitting mothers are those who seroconvert in pregnancy or who for social reasons are diagnosed late in pregnancy. As a result, now, genes associated with poor immune control of HIV are not enriched in mothers who transmit HIV to their child. These changes will likely influence the effectiveness of HLA-associated immune responses and therefore cure potential among children.
影响因子：
3.7
作者：
Matthews PC;Listgarten J;Carlson JM;Payne R;Huang KH;Frater J;Goedhals D;Steyn D;van Vuuren C;Paioni P;Jooste P;Ogwu A;Shapiro R;Mncube Z;Ndung'u T;Walker BD;Heckerman D;Goulder PJ
通讯作者：
Goulder PJ
DOI：
10.1084/jem.20080569
发表时间：
2008-05-12
期刊：
The Journal of experimental medicine
影响因子：
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作者：
Allen TM;Altfeld M
通讯作者：
Altfeld M