Infection of T cell subsets by HIV-1 and the effects of interleukin-12.
Infection of T cell subsets by HIV-1 and the effects of interleukin-12.
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HIV-1 对 T 细胞亚群的感染以及白细胞介素 12 的影响。
DOI：
10.1089/jir.1998.18.521
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Henderson,EE
中科院分区：
文献类型：
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作者：
Salgame,P;Guan,MX;Agahtehrani,A;Henderson,EE
CD 4+淋巴细胞是人类免疫缺陷病毒1型（HIV 1）感染的主要细胞靶点之一。CD 4+淋巴细胞的最终丧失在很大程度上促进了HIV-1的发病机制和获得性免疫缺陷综合征（AIDS）的发展。CD 4+淋巴细胞由Th 1、Th 2和Th 0亚群组成，它们的细胞因子谱不同。Thl细胞产生有利于细胞介导的免疫应答的细胞因子，而Th 2细胞产生有利于体液免疫的细胞因子。Th 0细胞是Th 1和Th 2亚群的前体。已经报道了HIV-1感染患者从Th 1到Th 2应答的转变（Kannagi等，1990.J.Virol.64，3399-3406;步行者等，1986.Science234，1563-1566;步行者等，1991.J.Virol.65，5921-5927）。由于这个原因，细胞因子在艾滋病发展中的潜在作用受到了极大的关注。白细胞介素（IL）-12是由抗原呈递细胞产生的二硫键连接的70-kDa异源二聚体细胞因子。IL-12在Thl型免疫应答的发展中具有中心作用。因此，我们研究了T嗜性HIV-1 IIIB在Th 1、Th 2和Th 0 T细胞克隆中复制的能力，并研究了IL-12对这些细胞类型中HIV-1复制的影响。这些研究表明了几点。(1)Th 1、Th 2和Th 0 T细胞克隆几乎同样支持HIV-1 IIIB复制，因此，支持HIV-1复制能力的差异不太可能解释HIV-1感染后Th 1、Th 2或Th 0亚型1的变化。(2)使用该模型，我们表明IL-12可以抑制HIV-1复制，这与IL-12在T细胞中HIV-1复制中的作用一致。(3)HIV-1可以在T细胞克隆中形成持续感染，为研究病毒避难所和在非常接近其体内情况的系统中的持续性提供了一个水库模型。
CD4+lymphocytes constitute one of the major cell targets for human immunodeficiency virus type 1 (HIV1) infection. The eventual loss of CD4+lymphocytes contributes substantially to the pathogensis of HIV-1 and development of acquired immunodeficiency syndrome (AIDS). CD4+lymphocytes consist of the subgroups Thl, Th2, and Th0, which differ in their cytokine profile. Thl cells produce cytokines that favor cell-mediated immune responses, whereas Th2 cells produce cytokines that favor humoral immunity. Th0 cells are precursors to the Thl and Th2 subsets. A shift from a Thl to a Th2 response has been reported for HIV-1-infected patients (Kannagi et al. 1990.J. Virol.64, 3399–3406; Walker et al. 1986.Science234, 1563–1566; Walker et al. 1991.J. Virol.65, 5921–5927). For this reason, the potential role of cytokines in the development of AIDS has received a great deal of attention. Interleukin (IL)-12 is a disulfide-linked, 70-kDa heterodimeric cytokine produced by antigen-presenting cells. IL-12 has a central role in the development of the Thl-type immune responses. Therefore, we investigated the ability of T-tropic HIV-1 IIIB to replicate in Thl, Th2, and Th0 T cell clones and studied the effects of IL-12 on HIV-1 replication in these cells types. These studies demonstrate several points. (1) Thl, Th2, and Th0 T cell clones support HIV-1 IIIB replication nearly equally well, and it is, therefore, unlikely that differences in ability to support HIV-1 replication can explain changes in Thl, Th2, or Th0 subtype 1 following HIV-1 infection. (2) Using this model, we show that IL-12 can inhibit HIV-1 replication, consistent with a role for IL-12 in HIV-1 replication in T cells. (3) HIV-1 can form a persistent infection in T cell clones, providing a reservoir model for study of viral sanctuary and persistence in a system closely approximating thein vivosituation.