Cell-Extrinsic Priming Increases Permissiveness of CD4+ T Cells to Human Immunodeficiency Virus Infection by Increasing C–C Chemokine Receptor Type 5 Co-receptor Expression and Cellular Activation Status

The chemokine receptor CCR5 is expressed on multiple cell types, including macrophages, dendritic cells, and T cells, and is the major co-receptor used during HIV transmission. Using a standard αCD3/CD28 in vitro stimulation protocol to render CD4+ T cells from PBMCs permissive to HIV infection, we...

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Autores principales:	Jesper G. Pedersen, Johanne H. Egedal, Thomas A. Packard, Karthiga Thavachelvam, Guorui Xie, Renée Marije van der Sluis, Warner C. Greene, Nadia R. Roan, Martin R. Jakobsen
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	human immunodeficiency virus (HIV) CD4 T cell priming CCR5 PD-1 Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/645cdc5c0c3440dcb09dfb4688ca1a1b
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spelling	oai:doaj.org-article:645cdc5c0c3440dcb09dfb4688ca1a1b2021-12-01T07:16:55ZCell-Extrinsic Priming Increases Permissiveness of CD4+ T Cells to Human Immunodeficiency Virus Infection by Increasing C–C Chemokine Receptor Type 5 Co-receptor Expression and Cellular Activation Status1664-302X10.3389/fmicb.2021.763030https://doaj.org/article/645cdc5c0c3440dcb09dfb4688ca1a1b2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmicb.2021.763030/fullhttps://doaj.org/toc/1664-302XThe chemokine receptor CCR5 is expressed on multiple cell types, including macrophages, dendritic cells, and T cells, and is the major co-receptor used during HIV transmission. Using a standard αCD3/CD28 in vitro stimulation protocol to render CD4+ T cells from PBMCs permissive to HIV infection, we discovered that the percentage of CCR5+ T cells was significantly elevated in CD4+ T cells when stimulated in the presence of peripheral blood mononuclear cells (PBMCs) as compared to when stimulated as purified CD4+ T cells. This indicated that environmental factors unique to the T-PBMCs condition affect surface expression of CCR5 on CD4+ T cells. Conditioned media from αCD3/CD28-stimulated PBMCs induced CCR5 expression in cultures of unstimulated cells. Cytokine profile analysis of these media suggests IL-12 as an inducer of CCR5 expression. Mass cytometric analysis showed that stimulated T-PBMCs exhibited a uniquely activated phenotype compared to T-Pure. In line with increased CCR5 expression and activation status in stimulated T-PBMCs, CD4+ T cells from these cultures were more susceptible to infection by CCR5-tropic HIV-1 as compared with T-Pure cells. These results suggest that in order to increase ex vivo infection rates of blood-derived CD4+ T cells, standard stimulation protocols used in HIV infection studies should implement T-PBMCs or purified CD4+ T cells should be supplemented with IL-12.Jesper G. PedersenJohanne H. EgedalJohanne H. EgedalThomas A. PackardKarthiga ThavachelvamGuorui XieGuorui XieRenée Marije van der SluisRenée Marije van der SluisWarner C. GreeneNadia R. RoanNadia R. RoanMartin R. JakobsenFrontiers Media S.A.articlehuman immunodeficiency virus (HIV)CD4 T cellprimingCCR5PD-1MicrobiologyQR1-502ENFrontiers in Microbiology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	human immunodeficiency virus (HIV) CD4 T cell priming CCR5 PD-1 Microbiology QR1-502
spellingShingle	human immunodeficiency virus (HIV) CD4 T cell priming CCR5 PD-1 Microbiology QR1-502 Jesper G. Pedersen Johanne H. Egedal Johanne H. Egedal Thomas A. Packard Karthiga Thavachelvam Guorui Xie Guorui Xie Renée Marije van der Sluis Renée Marije van der Sluis Warner C. Greene Nadia R. Roan Nadia R. Roan Martin R. Jakobsen Cell-Extrinsic Priming Increases Permissiveness of CD4+ T Cells to Human Immunodeficiency Virus Infection by Increasing C–C Chemokine Receptor Type 5 Co-receptor Expression and Cellular Activation Status
description	The chemokine receptor CCR5 is expressed on multiple cell types, including macrophages, dendritic cells, and T cells, and is the major co-receptor used during HIV transmission. Using a standard αCD3/CD28 in vitro stimulation protocol to render CD4+ T cells from PBMCs permissive to HIV infection, we discovered that the percentage of CCR5+ T cells was significantly elevated in CD4+ T cells when stimulated in the presence of peripheral blood mononuclear cells (PBMCs) as compared to when stimulated as purified CD4+ T cells. This indicated that environmental factors unique to the T-PBMCs condition affect surface expression of CCR5 on CD4+ T cells. Conditioned media from αCD3/CD28-stimulated PBMCs induced CCR5 expression in cultures of unstimulated cells. Cytokine profile analysis of these media suggests IL-12 as an inducer of CCR5 expression. Mass cytometric analysis showed that stimulated T-PBMCs exhibited a uniquely activated phenotype compared to T-Pure. In line with increased CCR5 expression and activation status in stimulated T-PBMCs, CD4+ T cells from these cultures were more susceptible to infection by CCR5-tropic HIV-1 as compared with T-Pure cells. These results suggest that in order to increase ex vivo infection rates of blood-derived CD4+ T cells, standard stimulation protocols used in HIV infection studies should implement T-PBMCs or purified CD4+ T cells should be supplemented with IL-12.
format	article
author	Jesper G. Pedersen Johanne H. Egedal Johanne H. Egedal Thomas A. Packard Karthiga Thavachelvam Guorui Xie Guorui Xie Renée Marije van der Sluis Renée Marije van der Sluis Warner C. Greene Nadia R. Roan Nadia R. Roan Martin R. Jakobsen
author_facet	Jesper G. Pedersen Johanne H. Egedal Johanne H. Egedal Thomas A. Packard Karthiga Thavachelvam Guorui Xie Guorui Xie Renée Marije van der Sluis Renée Marije van der Sluis Warner C. Greene Nadia R. Roan Nadia R. Roan Martin R. Jakobsen
author_sort	Jesper G. Pedersen
title	Cell-Extrinsic Priming Increases Permissiveness of CD4+ T Cells to Human Immunodeficiency Virus Infection by Increasing C–C Chemokine Receptor Type 5 Co-receptor Expression and Cellular Activation Status
title_short	Cell-Extrinsic Priming Increases Permissiveness of CD4+ T Cells to Human Immunodeficiency Virus Infection by Increasing C–C Chemokine Receptor Type 5 Co-receptor Expression and Cellular Activation Status
title_full	Cell-Extrinsic Priming Increases Permissiveness of CD4+ T Cells to Human Immunodeficiency Virus Infection by Increasing C–C Chemokine Receptor Type 5 Co-receptor Expression and Cellular Activation Status
title_fullStr	Cell-Extrinsic Priming Increases Permissiveness of CD4+ T Cells to Human Immunodeficiency Virus Infection by Increasing C–C Chemokine Receptor Type 5 Co-receptor Expression and Cellular Activation Status
title_full_unstemmed	Cell-Extrinsic Priming Increases Permissiveness of CD4+ T Cells to Human Immunodeficiency Virus Infection by Increasing C–C Chemokine Receptor Type 5 Co-receptor Expression and Cellular Activation Status
title_sort	cell-extrinsic priming increases permissiveness of cd4+ t cells to human immunodeficiency virus infection by increasing c–c chemokine receptor type 5 co-receptor expression and cellular activation status
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/645cdc5c0c3440dcb09dfb4688ca1a1b
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Cell-Extrinsic Priming Increases Permissiveness of CD4+ T Cells to Human Immunodeficiency Virus Infection by Increasing C–C Chemokine Receptor Type 5 Co-receptor Expression and Cellular Activation Status

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