Selective Loss of Early Differentiated, Highly Functional PD1high CD4 T Cells with HIV Progression.
The role of PD-1 expression on CD4 T cells during HIV infection is not well understood. Here, we describe the differential expression of PD-1 in CD127high CD4 T cells within the early/intermediate differentiated (EI) (CD27highCD45RAlow) T cell population among uninfected and HIV-infected subjects, w...
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doaj-01e8ec19c6c6413cbee3716288fb569e2020-11-25T00:59:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011012e014476710.1371/journal.pone.0144767Selective Loss of Early Differentiated, Highly Functional PD1high CD4 T Cells with HIV Progression.Robert M ParisConstantinos PetrovasSara Ferrando-MartinezEirini MoysiKristin L BoswellEva ArcherTakuya YamamotoDavid AmbrozakJoseph P CasazzaRichard HaubrichMark ConnorsJulie AkeJerome H KimRichard A KoupThe role of PD-1 expression on CD4 T cells during HIV infection is not well understood. Here, we describe the differential expression of PD-1 in CD127high CD4 T cells within the early/intermediate differentiated (EI) (CD27highCD45RAlow) T cell population among uninfected and HIV-infected subjects, with higher expression associated with decreased viral replication (HIV-1 viral load). A significant loss of circulating PD-1highCTLA-4low CD4 T cells was found specifically in the CD127highCD27highCD45RAlow compartment, while initiation of antiretroviral treatment, particularly in subjects with advanced disease, reversed these dynamics. Increased HIV-1 Gag DNA was also found in PD-1high compared to PD-1low ED CD4 T cells. In line with an increased susceptibility to HIV infection, PD-1 expression in this CD4 T cell subset was associated with increased activation and expression of the HIV co-receptor, CCR5. Rather than exhaustion, this population produced more IFN-g, MIP1-a, IL-4, IL-10, and IL-17a compared to PD-1low EI CD4 T cells. In line with our previous findings, PD-1high EI CD4 T cells were also characterized by a high expression of CCR7, CXCR5 and CCR6, a phenotype associated with increased in vitro B cell help. Our data show that expression of PD-1 on early-differentiated CD4 T cells may represent a population that is highly functional, more susceptible to HIV infection and selectively lost in chronic HIV infection.http://europepmc.org/articles/PMC4692060?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Robert M Paris Constantinos Petrovas Sara Ferrando-Martinez Eirini Moysi Kristin L Boswell Eva Archer Takuya Yamamoto David Ambrozak Joseph P Casazza Richard Haubrich Mark Connors Julie Ake Jerome H Kim Richard A Koup |
spellingShingle |
Robert M Paris Constantinos Petrovas Sara Ferrando-Martinez Eirini Moysi Kristin L Boswell Eva Archer Takuya Yamamoto David Ambrozak Joseph P Casazza Richard Haubrich Mark Connors Julie Ake Jerome H Kim Richard A Koup Selective Loss of Early Differentiated, Highly Functional PD1high CD4 T Cells with HIV Progression. PLoS ONE |
author_facet |
Robert M Paris Constantinos Petrovas Sara Ferrando-Martinez Eirini Moysi Kristin L Boswell Eva Archer Takuya Yamamoto David Ambrozak Joseph P Casazza Richard Haubrich Mark Connors Julie Ake Jerome H Kim Richard A Koup |
author_sort |
Robert M Paris |
title |
Selective Loss of Early Differentiated, Highly Functional PD1high CD4 T Cells with HIV Progression. |
title_short |
Selective Loss of Early Differentiated, Highly Functional PD1high CD4 T Cells with HIV Progression. |
title_full |
Selective Loss of Early Differentiated, Highly Functional PD1high CD4 T Cells with HIV Progression. |
title_fullStr |
Selective Loss of Early Differentiated, Highly Functional PD1high CD4 T Cells with HIV Progression. |
title_full_unstemmed |
Selective Loss of Early Differentiated, Highly Functional PD1high CD4 T Cells with HIV Progression. |
title_sort |
selective loss of early differentiated, highly functional pd1high cd4 t cells with hiv progression. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2015-01-01 |
description |
The role of PD-1 expression on CD4 T cells during HIV infection is not well understood. Here, we describe the differential expression of PD-1 in CD127high CD4 T cells within the early/intermediate differentiated (EI) (CD27highCD45RAlow) T cell population among uninfected and HIV-infected subjects, with higher expression associated with decreased viral replication (HIV-1 viral load). A significant loss of circulating PD-1highCTLA-4low CD4 T cells was found specifically in the CD127highCD27highCD45RAlow compartment, while initiation of antiretroviral treatment, particularly in subjects with advanced disease, reversed these dynamics. Increased HIV-1 Gag DNA was also found in PD-1high compared to PD-1low ED CD4 T cells. In line with an increased susceptibility to HIV infection, PD-1 expression in this CD4 T cell subset was associated with increased activation and expression of the HIV co-receptor, CCR5. Rather than exhaustion, this population produced more IFN-g, MIP1-a, IL-4, IL-10, and IL-17a compared to PD-1low EI CD4 T cells. In line with our previous findings, PD-1high EI CD4 T cells were also characterized by a high expression of CCR7, CXCR5 and CCR6, a phenotype associated with increased in vitro B cell help. Our data show that expression of PD-1 on early-differentiated CD4 T cells may represent a population that is highly functional, more susceptible to HIV infection and selectively lost in chronic HIV infection. |
url |
http://europepmc.org/articles/PMC4692060?pdf=render |
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