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Identification of a CCR5-Expressing T Cell Subset That Is Resistant to R5-Tropic HIV Infection

Infection with HIV-1 perturbs homeostasis of human T cell subsets, leading to accelerated immunologic deterioration. While studying changes in CD4(+) memory and naïve T cells during HIV-1 infection, we found that a subset of CD4(+) effector memory T cells that are CCR7(−)CD45RO(−)CD45RA(+) (referred...

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Autores principales: Oswald-Richter, Kyra, Grill, Stacy M, Leelawong, Mindy, Tseng, Michelle, Kalams, Spyros A, Hulgan, Todd, Haas, David W, Unutmaz, Derya
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1857714/
https://www.ncbi.nlm.nih.gov/pubmed/17465678
http://dx.doi.org/10.1371/journal.ppat.0030058
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author Oswald-Richter, Kyra
Grill, Stacy M
Leelawong, Mindy
Tseng, Michelle
Kalams, Spyros A
Hulgan, Todd
Haas, David W
Unutmaz, Derya
author_facet Oswald-Richter, Kyra
Grill, Stacy M
Leelawong, Mindy
Tseng, Michelle
Kalams, Spyros A
Hulgan, Todd
Haas, David W
Unutmaz, Derya
author_sort Oswald-Richter, Kyra
collection PubMed
description Infection with HIV-1 perturbs homeostasis of human T cell subsets, leading to accelerated immunologic deterioration. While studying changes in CD4(+) memory and naïve T cells during HIV-1 infection, we found that a subset of CD4(+) effector memory T cells that are CCR7(−)CD45RO(−)CD45RA(+) (referred to as T(EMRA) cells), was significantly increased in some HIV-infected individuals. This T cell subset displayed a differentiated phenotype and skewed Th1-type cytokine production. Despite expressing high levels of CCR5, T(EMRA) cells were strikingly resistant to infection with CCR5 (R5)–tropic HIV-1, but remained highly susceptible to CXCR4 (X4)–tropic HIV-1. The resistance of T(EMRA) cells to R5-tropic viruses was determined to be post-entry of the virus and prior to early viral reverse transcription, suggesting a block at the uncoating stage. Remarkably, in a subset of the HIV-infected individuals, the relatively high proportion of T(EMRA) cells within effector T cells strongly correlated with higher CD4(+) T cell numbers. These data provide compelling evidence for selection of an HIV-1–resistant CD4(+) T cell population during the course of HIV-1 infection. Determining the host factors within T(EMRA) cells that restrict R5-tropic viruses and endow HIV-1–specific CD4(+) T cells with this ability may result in novel therapeutic strategies against HIV-1 infection.
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spelling pubmed-18577142007-04-27 Identification of a CCR5-Expressing T Cell Subset That Is Resistant to R5-Tropic HIV Infection Oswald-Richter, Kyra Grill, Stacy M Leelawong, Mindy Tseng, Michelle Kalams, Spyros A Hulgan, Todd Haas, David W Unutmaz, Derya PLoS Pathog Research Article Infection with HIV-1 perturbs homeostasis of human T cell subsets, leading to accelerated immunologic deterioration. While studying changes in CD4(+) memory and naïve T cells during HIV-1 infection, we found that a subset of CD4(+) effector memory T cells that are CCR7(−)CD45RO(−)CD45RA(+) (referred to as T(EMRA) cells), was significantly increased in some HIV-infected individuals. This T cell subset displayed a differentiated phenotype and skewed Th1-type cytokine production. Despite expressing high levels of CCR5, T(EMRA) cells were strikingly resistant to infection with CCR5 (R5)–tropic HIV-1, but remained highly susceptible to CXCR4 (X4)–tropic HIV-1. The resistance of T(EMRA) cells to R5-tropic viruses was determined to be post-entry of the virus and prior to early viral reverse transcription, suggesting a block at the uncoating stage. Remarkably, in a subset of the HIV-infected individuals, the relatively high proportion of T(EMRA) cells within effector T cells strongly correlated with higher CD4(+) T cell numbers. These data provide compelling evidence for selection of an HIV-1–resistant CD4(+) T cell population during the course of HIV-1 infection. Determining the host factors within T(EMRA) cells that restrict R5-tropic viruses and endow HIV-1–specific CD4(+) T cells with this ability may result in novel therapeutic strategies against HIV-1 infection. Public Library of Science 2007-04 2007-04-27 /pmc/articles/PMC1857714/ /pubmed/17465678 http://dx.doi.org/10.1371/journal.ppat.0030058 Text en © 2007 Oswald-Richter et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Oswald-Richter, Kyra
Grill, Stacy M
Leelawong, Mindy
Tseng, Michelle
Kalams, Spyros A
Hulgan, Todd
Haas, David W
Unutmaz, Derya
Identification of a CCR5-Expressing T Cell Subset That Is Resistant to R5-Tropic HIV Infection
title Identification of a CCR5-Expressing T Cell Subset That Is Resistant to R5-Tropic HIV Infection
title_full Identification of a CCR5-Expressing T Cell Subset That Is Resistant to R5-Tropic HIV Infection
title_fullStr Identification of a CCR5-Expressing T Cell Subset That Is Resistant to R5-Tropic HIV Infection
title_full_unstemmed Identification of a CCR5-Expressing T Cell Subset That Is Resistant to R5-Tropic HIV Infection
title_short Identification of a CCR5-Expressing T Cell Subset That Is Resistant to R5-Tropic HIV Infection
title_sort identification of a ccr5-expressing t cell subset that is resistant to r5-tropic hiv infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1857714/
https://www.ncbi.nlm.nih.gov/pubmed/17465678
http://dx.doi.org/10.1371/journal.ppat.0030058
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