Preferential infection shortens the life span of human immunodeficiency virus-specific CD4+ T cells in vivo
Preferential infection shortens the life span of human immunodeficiency virus-specific CD4+ T cells in vivo
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DOI：
10.1128/jvi.00070-06
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发表时间：
2006-07-01
影响因子：
5.4
通讯作者：
Douek, Daniel C.
中科院分区：
文献类型：
--
作者：
Brenchley, Jason M.;Ruff, Laura E.;Douek, Daniel C.
CD4(+) t细胞的帮助对于有效的病毒免疫反应是必不可少的。在人类免疫缺陷病毒（HIV）感染中，HIV特异性CD4(+) T细胞被病毒感染的频率高于其他记忆性CD4(+) T细胞。在这里，我们证明hiv特异性CD4(+) T细胞在大多数感染个体中几乎检测不到，并且与巨细胞病毒（CMV）特异性CD4(+) T细胞和其他记忆性CD4(+) T细胞相比，相应的CD4(+) T细胞表现出不成熟的表型。然而，在两个个体中，我们观察到一种罕见的、截然相反的模式，即hiv特异性CD4(+) t细胞群表现出一种终末分化的免疫表型；这些细胞在体内没有被优先感染。克隆型分析显示，来自这些个体的hiv特异性CD4(+) T细胞与CMV交叉反应。因此，在交叉反应的CD4(+) T细胞通过共同感染病毒抗原驱动成熟的情况下，可以避免优先感染，这种物理接近性而不是激活状态本身是基于抗原特异性的优先感染的重要决定因素。这些数据表明，优先感染减少了体内hiv特异性CD4(+) T细胞的寿命，从而损害了对病毒本身产生有效免疫反应的能力；此外，HIV感染病理生理学的这一核心特征可能受到CD4(+) T细胞交叉反应的影响。
CD4(+) T-cell help is essential for effective immune responses to viruses. In human immunodeficiency virus (HIV) infection, CD4(+) T cells specific for HIV are infected by the virus at higher frequencies than other memory CD4(+) T cells. Here, we demonstrate that HIV-specific CD4(+) T cells are barely detectable in most infected individuals and that the corresponding CD4(+) T cells exhibit an immature phenotype compared to both cytomegalovirus (CMV)-specific CD4(+) T cells and other memory CD4(+) T cells. However, in two individuals, we observed a rare and diametrically opposed pattern in which HIV-specific CD4(+) T-cell populations of large magnitude exhibited a terminally differentiated immunophenotype; these cells were not preferentially infected in vivo. Clonotypic analysis revealed that the HIV-specific CD4(+) T cells from these individuals were cross-reactive with CMV. Thus, preferential infection can be circumvented in the presence of cross-reactive CD4(+) T cells driven to maturity by coinfecting viral antigens, and this physical proximity rather than activation status per se is an important determinant of preferential infection based on antigen specificity. These data demonstrate that preferential infection reduces the life span of HIV-specific CD4(+) T cells in vivo and thereby compromises the generation of effective immune responses to the virus itself; further, this central feature in the pathophysiology of HIV infection can be influenced by the cross-reactivity of responding CD4(+) T cells.