Both memory and CD45RA+/CD62L+ naive CD4+ T cells are infected in human immunodeficiency virus type 1-infected individuals
Both memory and CD45RA+/CD62L+ naive CD4+ T cells are infected in human immunodeficiency virus type 1-infected individuals
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DOI：
10.1128/jvi.73.8.6430-6435.1999
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发表时间：
1999-08-01
影响因子：
5.4
通讯作者：
Fauci, AS
中科院分区：
文献类型：
--
作者：
Ostrowski, MA;Chun, TW;Fauci, AS
细胞激活对于 1 型人类免疫缺陷病毒 (HIV-1) 感染的传播至关重要。有人认为，真正幼稚的CD4(+) T 细胞由于其固有的静息状态而对生产性HIV-1 感染具有抵抗力。通过磁珠去除和荧光激活细胞分选技术相结合，结合 CD45RA 和 CD62L 联合表达的严格标准，离体分离 11 名 HIV-1 感染者的记忆和幼稚 CD4(+) T 细胞亚群，以鉴定幼稚 CD4(+) T 细胞亚群。在所有患者中，在初始 CD45RA(+)/CD62L(+) CD4(+) T 细胞中均可检测到 HIV-1 原病毒；此外，在组织培养中刺激CD4(+) T细胞后，可以从这些细胞中分离出具有复制能力的HIV-1。记忆CD4(+) T细胞的复制能力病毒中位数比初始CD4(+) T细胞多四倍，原病毒中位数比幼稚CD4(+) T细胞多六倍。总体而言，在给定患者中，记忆CD4(+) T细胞中鉴定出的整合原病毒中值比幼稚CD4(+) T细胞中多16倍。有趣的是，在那些携带CXCR4（合胞体诱导）病毒的患者中，记忆和幼稚CD4（+）T细胞亚群中的病毒载量有趋于均衡的趋势。在任何给定的患者中，从记忆中分离出的病毒与初始CD4(+) T细胞相比，没有选择性地使用特定的辅助受体。我们的研究结果表明，初始 CD4(+) T 细胞可能是 HIV 的重要病毒库，特别是在那些携带 CXCR4 使用病毒的患者中。
Cellular activation is critical for the propagation of human immunodeficiency virus type 1 (HIV-1) infection. It has been suggested that truly naive CD4(+) T cells are resistant to productive HIV-1 infection because of their constitutive resting state. Memory and naive CD4(+) T-cell subsets from 11 HIV-1-infected individuals were isolated ex vivo by a combination of magnetic bead depletion and fluorescence-activated cell sorting techniques with stringent criteria of combined expression of CD45RA and CD62L to identify naive CD4(+) T-cell subsets. In all patients HIV-1 provirus could be detected within naive CD45RA(+)/CD62L(+) CD4(+) T cells; in addition, replication-competent HIV-1 was isolated from these cells upon CD4(+) T-cell stimulation in tissue cultures. Memory CD4(+) T cells had a median of fourfold more replication-competent virus and a median of sixfold more provirus than naive CD4(+) T cells. Overall, there was a median of 16-fold more integrated provirus identified in memory CD4(+) T cells than in naive CD4(+) T cells within a given patient. Interestingly, there was a trend toward equalization of viral loads in memory and naive CD4(+) T-cell subsets in those patients who harbored CXCR4-using (syncytium-inducing) viruses. Within any given patient, there was no selective usage of a particular coreceptor by virus isolated from memory versus naive CD4(+) T cells. Our findings suggest that naive CD4(+) T cells may be a significant viral reservoir for HIV, particularly in those patients harboring CXCR4-using viruses.