Immunologic characteristics of HIV-infected individuals who make broadly neutralizing antibodies.
Immunologic characteristics of HIV-infected individuals who make broadly neutralizing antibodies.
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DOI：
10.1111/imr.12504
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发表时间：
2017-01
影响因子：
8.7
通讯作者：
Moody MA
中科院分区：
文献类型：
--
作者：
Borrow P;Moody MA
诱导能够抑制人类免疫缺陷病毒1型（HIV-1）不同变体感染的广泛中和抗体（bnAb）是预防性HIV-1疫苗策略的一个关键但尚未实现的目标。然而，一些HIV感染者在感染约2 - 4年后会产生bnAbs，从而能够分析这些抗体的特征以及能够诱导它们的免疫环境。不同的CD 4 + T细胞亚群在体液应答的调节中起着相反的作用：T滤泡辅助细胞（Tfh）支持生发中心的形成，并为亲和力成熟和记忆B细胞和浆细胞的发育提供帮助，而调节性CD 4+（Treg）细胞包括T滤泡调节细胞（Tfr）抑制生发中心反应以限制自身抗体的产生。BnAb表现出较高的体细胞突变频率、较长的第三重链互补决定区和/或自身反应性，表明bnAb的产生可能高度依赖于CD 4 + Tfh细胞的活性，并且可能受到宿主耐受性对照的限制。本综述讨论了HIV-1感染期间的免疫环境，特别是CD 4 + Tfh，Treg和Tfr群体和自身抗体产生的变化，以及这与bnAb开发的关系，并考虑了对HIV-1疫苗设计的影响。
Induction of broadly neutralizing antibodies (bnAbs) capable of inhibiting infection with diverse variants of human immunodeficiency virus type 1 (HIV‐1) is a key, as‐yet‐unachieved goal of prophylactic HIV‐1 vaccine strategies. However, some HIV‐infected individuals develop bnAbs after approximately 2‐4 years of infection, enabling analysis of features of these antibodies and the immunological environment that enables their induction. Distinct subsets of CD4+ T cells play opposing roles in the regulation of humoral responses: T follicular helper (Tfh) cells support germinal center formation and provide help for affinity maturation and the development of memory B cells and plasma cells, while regulatory CD4+ (Treg) cells including T follicular regulatory (Tfr) cells inhibit the germinal center reaction to limit autoantibody production. BnAbs exhibit high somatic mutation frequencies, long third heavy‐chain complementarity determining regions, and/or autoreactivity, suggesting that bnAb generation is likely to be highly dependent on the activity of CD4+ Tfh cells, and may be constrained by host tolerance controls. This review discusses what is known about the immunological environment during HIV‐1 infection, in particular alterations in CD4+ Tfh, Treg, and Tfr populations and autoantibody generation, and how this is related to bnAb development, and considers the implications for HIV‐1 vaccine design.