Roles for CXC chemokine ligands 10 and 11 in recruiting CD4+ T cells to HIV-1-infected monocyte-derived macrophages, dendritic cells, and lymph nodes
Roles for CXC chemokine ligands 10 and 11 in recruiting CD4+ T cells to HIV-1-infected monocyte-derived macrophages, dendritic cells, and lymph nodes
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DOI：
10.4049/jimmunol.174.8.4892
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发表时间：
2005-04-15
影响因子：
4.4
通讯作者：
Farber, JM
中科院分区：
文献类型：
--
作者：
Foley, JF;Yu, CR;Farber, JM
我们研究了化学引诱物在HIV-1传播中的作用，通过检测HIV-1感染的人单核细胞衍生的巨噬细胞和树突状细胞中T细胞活性趋化因子的诱导。在分析的12种趋化因子中，趋化因子受体CXCR 3的配体CXCL 10和CXCL 11的mRNA在HIV-1感染后在两种细胞类型中均上调。这些趋化因子基因在感染的培养物中的诱导依赖于病毒进入和逆转录酶活性，但不依赖于HIV-1包膜糖蛋白。感染细胞的条件培养基对新鲜分离的人CD 4（+）T细胞具有趋化性，用CXCR 3抗体预处理可消除趋化性。从HIV-1感染者的淋巴结表达CXCL 10和CXCL 11 mRNA的副皮质，包括小静脉，通过原位杂交检测，而既不是mRNA后检测到高活性的抗逆转录病毒治疗。由于CD 4（+）T细胞上的CCR 5主要存在于也表达CXCR 3的细胞上，因此这些数据暗示CXCL 10和CXCL 11参与了易感T细胞向HIV-1感染的淋巴结、巨噬细胞和树突状细胞的募集。这种募集可能会增强T细胞在受感染淋巴器官中的隔离以及细胞间感染的传播，从而促进艾滋病的免疫病理学。
We investigated roles for chemoattractants; in dissemination of HIV-1 by examining the induction of T cell-active chemokines in HIV-1-infected human monocyte-derived macrophages and dendritic cells. Of the 12 chemokines analyzed, mRNAs for two, CXCL10 and CXCL11, ligands for the chemokine receptor CXCR3, were up-regulated in both cell types upon infection by HIV-1. Induction of these chemokine genes in infected cultures was dependent on both viral entry and reverse transcriptase activity, but not on the HIV-1 envelope glycoprotein. Conditioned medium from infected cells was chemotactic for freshly isolated human CD4(+) T cells, and chemotaxis was abolished by pretreatment with an Ab against CXCR3. A lymph node from an HIV-1-infected individual expressed CXCL10 and CXCL11 mRNAs in the paracortex, including venules, as detected by in situ hybridization, whereas neither mRNA was detected after highly active antiretroviral therapy. Because CCR5 on CD4(+) T cells is found predominantly on cells that also express CXCR3, these data implicate CXCL10 and CXCL11 in the recruitment of susceptible T cells to HIV-1-infected lymph nodes, macrophages, and dendritic cells. This recruitment might enhance the sequestration of T cells in infected lymphoid organs and the spread of infection between cells, contributing to the immunopathology of AIDS.