CD40 ligand (CD154) stimulation of macrophages to produce HIV-1-suppressive β-chemokines
CD40 ligand (CD154) stimulation of macrophages to produce HIV-1-suppressive β-chemokines
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DOI：
10.1073/pnas.95.9.5205
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发表时间：
1998-04-28
影响因子：
11.1
通讯作者：
Richman, DD
中科院分区：
文献类型：
--
作者：
Kornbluth, RS;Kee, K;Richman, DD
β-趋化因子在免疫反应的发展中起重要作用。巨噬细胞是组织中T细胞介导的迟发型超敏反应期间主要的β-趋化因子产生细胞，并且据报道是HIV-1感染个体淋巴结中β-趋化因子的重要产生者。然而，负责诱导巨噬细胞产生β-趋化因子的生理信号尚未建立。两种可溶性T细胞产物，干扰素-γ和粒细胞-巨噬细胞集落刺激因子，被添加到培养的巨噬细胞中，但未能刺激巨噬细胞炎性蛋白-1 α和-1 β的产生;活化后调节，正常T细胞表达和分泌（RANTES）;或单核细胞趋化蛋白-1。相反，巨噬细胞和工程化表达CD 40 L的细胞之间的直接细胞-细胞接触（也称为CD 154）导致大量巨噬细胞炎性蛋白-1 α和-1 β以及RANTES的产生。（CCR 5的所有配体）和单核细胞趋化蛋白-1来自CD 40 L刺激的巨噬细胞的上清液保护CD 4（+）T细胞免受HIV-1的非合胞体诱导株（其使用CCR 5作为辅助受体）的感染。这些结果对肉芽肿性疾病以及动脉粥样硬化和多发性硬化等疾病具有意义，其中在产生β-趋化因子的富含巨噬细胞的病变中发现了CD 40 L细胞。总之，这些发现定义了一条将T细胞对抗原的特异性识别与巨噬细胞产生β-趋化因子联系起来的途径，该途径可能在抗HIV-1免疫和免疫反应或病变的发展中起作用。
beta-chemokines play an important role in the development of immunologic reactions. Macrophages are major beta-chemokine-producing cells during T-cell directed, delayed-type hypersensitivity reactions in tissues, and have been reported to be important producers of beta-chemokines in the lymph nodes of HIV-1-infected individuals. However, the physiological signals responsible for inducing macrophages to produce beta-chemokines have not been established. Two soluble T cell products, interferon-gamma and granulocyte-macrophage colony stimulating factor, were added to cultured macro phages, but failed to stimulate the production of macrophage inflammatory protein-1 alpha and -1 beta; regulated upon activation, normal T cell expressed and secreted (RANTES); or monocyte chemoattractant protein-1. Instead, direct cell-cell contact between macrophages and cells engineered to express CD40L (also known as CD154) resulted in the production of large amounts of macrophage inflammatory protein-1 alpha and -1 beta, and RANTES (all ligands for CCR5), and monocyte chemoattractant protein-1 (a ligand for CCR2), Supernatants from CD40L-stimulated macrophages protected CD4(+) T cells from infection by a nonsyncytium-inducing strain of HIV-1 (which uses CCR5 as a coreceptor). These results have implications for granulomatous diseases, and conditions such as atherosclerosis and multiple sclerosis, where CD40L-bearing cells have been found in the macrophage-rich lesions where beta-chemokines are being produced. Overall, these findings define a pathway linking the specific recognition of antigen by T cells to the production of beta-chemokines by macrophages, This pathway may play a role in anti-HIV-1 immunity and the development of immunologic reactions or lesions.