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CCR5 susceptibility to ligand-mediated down-modulation differs between human T lymphocytes and myeloid cells

Fox, James M
Kasprowicz, Richard
Signoret, Nathalie
Published in Journal of leukocyte biology. 2015, vol. 98, no. 1, p. 59-71
Abstract CCR5 is a chemokine receptor expressed on leukocytes and a coreceptor used by HIV-1 to enter CD4(+) T lymphocytes and macrophages. Stimulation of CCR5 by chemokines triggers internalization of chemokine-bound CCR5 molecules in a process called down-modulation, which contributes to the anti-HIV activity of chemokines. Recent studies have shown that CCR5 conformational heterogeneity influences chemokine-CCR5 interactions and HIV-1 entry in transfected cells or activated CD4(+) T lymphocytes. However, the effect of CCR5 conformations on other cell types and on the process of down-modulation remains unclear. We used mAbs, some already shown to detect distinct CCR5 conformations, to compare the behavior of CCR5 on in vitro generated human T cell blasts, monocytes and MDMs and CHO-CCR5 transfectants. All human cells express distinct antigenic forms of CCR5 not detected on CHO-CCR5 cells. The recognizable populations of CCR5 receptors exhibit different patterns of down-modulation on T lymphocytes compared with myeloid cells. On T cell blasts, CCR5 is recognized by all antibodies and undergoes rapid chemokine-mediated internalization, whereas on monocytes and MDMs, a pool of CCR5 molecules is recognized by a subset of antibodies and is not removed from the cell surface. We demonstrate that this cell surface-retained form of CCR5 responds to prolonged treatment with more-potent chemokine analogs and acts as an HIV-1 coreceptor. Our findings indicate that the regulation of CCR5 is highly specific to cell type and provide a potential explanation for the observation that native chemokines are less-effective HIV-entry inhibitors on macrophages compared with T lymphocytes.
PMID: 25957306
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Research group Hiv (835)
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FOX, James M et al. CCR5 susceptibility to ligand-mediated down-modulation differs between human T lymphocytes and myeloid cells. In: Journal of leukocyte biology, 2015, vol. 98, n° 1, p. 59-71. doi: 10.1189/jlb.2A0414-193RR https://archive-ouverte.unige.ch/unige:73898

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Deposited on : 2015-07-06

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