The HIV coreceptors CXCR4 and CCR5 are differentially expressed and regulated on human T lymphocytes
The HIV coreceptors CXCR4 and CCR5 are differentially expressed and regulated on human T lymphocytes
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DOI：
10.1073/pnas.94.5.1925
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发表时间：
1997-03-04
影响因子：
11.1
通讯作者：
Mackay, CR
中科院分区：
文献类型：
--
作者：
Bleul, CC;Wu, LJ;Mackay, CR
趋化因子受体CXCR 4和CCR 5作为HIV-1进入CD 4（+）细胞的辅助受体发挥作用。在HIV感染的早期阶段，病毒分离株倾向于使用CCR 5进行病毒进入，而后期分离株倾向于使用CXCR 4。这些趋化因子受体在T细胞亚群上的表达模式及其调节对AIDS发病机制和淋巴细胞再循环具有重要意义。针对CXCR 4的mAb 12 G5显示出对由SDF-1（CXCR 4的天然配体）诱导的趋化性和钙内流的部分抑制。12 G5主要染色外周血淋巴细胞的幼稚的、未活化的CD 26（低）CD 45 RA（+）CD 45 R 0（-）T淋巴细胞亚群。相反，对CCR 5，5C 7特异性的mAb染色的CD 26（高）CD 45 RA（低）CD 45 RO（+）T淋巴细胞，被认为代表先前活化/记忆细胞的亚群，在植物血凝素刺激和白细胞介素2引发期间，外周血单核细胞上CXCR 4表达迅速上调，并且对SDF-1的反应性同时增加，然而，CCR 5表达，在用白细胞介素2培养的12天中，T细胞活化仅逐渐增加，而用植物血凝素活化T细胞无效。总之，数据表明两种受体及其配体在淋巴细胞亚群通过淋巴和非淋巴组织的迁移中具有不同的功能。外周血T细胞中CXCR 4和CCR 5的大部分相互表达暗示了在HIV感染过程中T细胞亚群对T细胞系嗜性与巨噬细胞嗜性株的病毒进入的不同易感性。
The chemokine receptors CXCR4 and CCR5 function as coreceptors for HIV-1 entry into CD4(+) cells, During the early stages of HIV infection, viral isolates tend to use CCR5 for viral entry, while later isolates tend to use CXCR4. The pattern of expression of these chemokine receptors on T cell subsets and their regulation has important implications for AIDS pathogenesis and lymphocyte recirculation, A mAb to CXCR4, 12G5, showed partial inhibition of chemotaxis and calcium influx induced by SDF-1, the natural ligand of CXCR4. 12G5 stained predominantly the naive, unactivated CD26(low) CD45RA(+) CD45R0(-) T lymphocyte subset of peripheral blood lymphocytes. In contrast, a mAb specific for CCR5, 5C7, stained CD26(high) CD45RA(low) CD45RO(+) T lymphocytes, a subset thought to represent previously activated/memory cells, CXCR4 expression was rapidly up-regulated on peripheral blood mononuclear cells during phytohemagglutinin stimulation and interleukin 2 priming, and responsiveness to SDF-1 increased simultaneously, CCR5 expression, however, showed only a gradual increase over 12 days of culture with interleukin 2, while T cell activation with phytohemagglutinin was ineffective, Taken together, the data suggest distinct functions for the two receptors and their ligands in the migration of lymphocyte subsets through lymphoid and nonlymphoid tissues, Furthermore, the largely reciprocal expression of CXCR4 and CCR5 among peripheral blood T cells implies distinct susceptibility of T cell subsets to viral entry by T cell line-tropic versus macrophage-tropic strains during the course of HIV infection.