Immunity to HIV in Early Life.
Immunity to HIV in Early Life.
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DOI：
10.3389/fimmu.2014.00391
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发表时间：
2014
影响因子：
7.3
通讯作者：
Goulder PJ
中科院分区：
文献类型：
--
作者：
Muenchhoff M;Prendergast AJ;Goulder PJ
发育中的免疫系统适应于在子宫和出生后遇到过多的致病和非致病抗原，需要在保护性免疫和免疫耐受性之间保持良好的平衡。在生命的早期阶段，这种先天和适应性免疫系统的耐受性状态以及免疫记忆的缺乏使宿主更容易受到艾滋病毒等传染性病原体的影响。与成人相比，儿童艾滋病毒的发病机制不同，疾病进展更快，与成人相比，病毒血症基本上缺乏控制。血浆病毒载量在婴儿期仍然很高，只是随着免疫成熟而在几年内逐渐下降，即使在极少数情况下，儿童在没有抗逆转录病毒治疗(ART)的情况下几年保持正常的CD4T淋巴细胞计数。这些儿科进展缓慢的患者通常也表现出低水平的免疫激活，尽管持续存在高病毒血症，类似于SIV感染的自然宿主的表型。免疫记忆力的缺乏使胎儿和新生儿面临更高的感染风险；然而，这也可能提供了进行独特干预的机会。中心记忆中的CD4+T淋巴细胞是HIV的主要细胞库之一，在新生儿中，其频率非常低，因此立即进行抗逆转录病毒治疗可以防止持续病毒库的建立，并导致“功能治愈”。然而，正如最近“密西西比州儿童”的病例报告所表明的那样，他在停用ART超过2年 后经历了病毒反弹，可能需要额外的免疫调节策略来维持ART停用后的病毒抑制。在这篇综述中，我们讨论了HIV与儿童发育中的免疫系统之间的相互作用，以及对治疗和预防干预的潜在影响。
The developing immune system is adapted to the exposure to a plethora of pathogenic and non-pathogenic antigens encountered in utero and after birth, requiring a fine balance between protective immunity and immune tolerance. In early stages of life, this tolerogenic state of the innate and adaptive immune system and the lack of immunological memory render the host more susceptible to infectious pathogens like HIV. HIV pathogenesis is different in children, compared to adults, with more rapid disease progression and a substantial lack of control of viremia compared to adults. Plasma viral load remains high during infancy and only declines gradually over several years in line with immune maturation, even in rare cases where children maintain normal CD4 T-lymphocyte counts for several years without antiretroviral therapy (ART). These pediatric slow progressors also typically show low levels of immune activation despite persistently high viremia, resembling the phenotype of natural hosts of SIV infection. The lack of immunological memory places the fetus and the newborn at higher risk of infections; however, it may also provide an opportunity for unique interventions. Frequencies of central memory CD4+ T-lymphocytes, one of the main cellular reservoirs of HIV, are very low in the newborn child, so immediate ART could prevent the establishment of persistent viral reservoirs and result in “functional cure.” However, as recently demonstrated in the case report of the “Mississippi child” who experienced viral rebound after more than 2 years off ART, additional immunomodulatory strategies might be required for sustained viral suppression after ART cessation. In this review, we discuss the interactions between HIV and the developing immune system in children and the potential implications for therapeutic and prophylactic interventions.
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DOI：
10.1016/j.clim.2009.07.003
发表时间：
2009-11
期刊：
Clinical immunology (Orlando, Fla.)
影响因子：
--
作者：
Belderbos ME;van Bleek GM;Levy O;Blanken MO;Houben ML;Schuijff L;Kimpen JL;Bont L
通讯作者：
Bont L
影响因子：
168.9
作者：
Babiker, A;Darby, S;Schechter, M
通讯作者：
Schechter, M
DOI：
10.1097/qai.0b013e318224d2e9
发表时间：
2011-10-01
影响因子：
3.6
作者：
Akinsiku, Olusimidele T.;Bansal, Anju;Goepfert, Paul A.
通讯作者：
Goepfert, Paul A.
影响因子：
30.5
作者：
Blackburn, Shawn D.;Shin, Haina;Haining, W. Nicholas;Zou, Tao;Workman, Creg J.;Polley, Antonio;Betts, Michael R.;Freeman, Gordon J.;Vignali, Dario A. A.;Wherry, E. John
通讯作者：
Wherry, E. John
影响因子：
4.4
作者：
Adkins, P;Bu, YR;Guevara, P
通讯作者：
Guevara, P