Progressive activation of CD127+132- recent thymic emigrants into terminally differentiated CD127-132+ T-cells in HIV-1 infection.
<h4>Aim</h4>HIV infection is associated with distortion of T-cell homeostasis and the IL-7/IL7R axis. Progressive infection results in loss of CD127+132- and gains in CD127-132+ CD4+ and CD8+ T-cells. We investigated the correlates of loss of CD127 from the T-cell surface to understand m...
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2012
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oai:doaj.org-article:82ee42fdf8e24afc9cd709cad2d3c6642021-11-18T07:28:27ZProgressive activation of CD127+132- recent thymic emigrants into terminally differentiated CD127-132+ T-cells in HIV-1 infection.1932-620310.1371/journal.pone.0031148https://doaj.org/article/82ee42fdf8e24afc9cd709cad2d3c6642012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22348045/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Aim</h4>HIV infection is associated with distortion of T-cell homeostasis and the IL-7/IL7R axis. Progressive infection results in loss of CD127+132- and gains in CD127-132+ CD4+ and CD8+ T-cells. We investigated the correlates of loss of CD127 from the T-cell surface to understand mechanisms underlying this homeostatic dysregulation.<h4>Methods</h4>Peripheral and cord blood mononuclear cells (PBMCs; CBMC) from healthy volunteers and PBMC from patients with HIV infection were studied. CD127+132-, CD127+132+ and CD127-132+ T-cells were phenotyped by activation, differentiation, proliferation and survival markers. Cellular HIV-DNA content and signal-joint T-cell receptor excision circles (sjTRECs) were measured.<h4>Results</h4>CD127+132- T-cells were enriched for naïve cells while CD127-132+ T-cells were enriched for activated/terminally differentiated T-cells in CD4+ and CD8+ subsets in health and HIV infection. HIV was associated with increased proportions of activated/terminally differentiated CD127-132+ T-cells. In contrast to CD127+132- T-cells, CD127-132+ T-cells were Ki-67+Bcl-2(low) and contained increased levels of HIV-DNA. Naïve CD127+132- T-cells contained a higher proportion of sjTRECs.<h4>Conclusion</h4>The loss of CD127 from the T-cell surface in HIV infection is driven by activation of CD127+132- recent thymic emigrants into CD127-132+ activated/terminally differentiated cells. This process likely results in an irreversible loss of CD127 and permanent distortion of T-cell homeostasis.Sarah C SassonJohn J ZaundersNabila SeddikiMichelle BaileyKristin McBrideKersten K KoelschKate M MerlinDon E SmithDavid A CooperAnthony D KelleherPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 2, p e31148 (2012) |
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Medicine R Science Q Sarah C Sasson John J Zaunders Nabila Seddiki Michelle Bailey Kristin McBride Kersten K Koelsch Kate M Merlin Don E Smith David A Cooper Anthony D Kelleher Progressive activation of CD127+132- recent thymic emigrants into terminally differentiated CD127-132+ T-cells in HIV-1 infection. |
description |
<h4>Aim</h4>HIV infection is associated with distortion of T-cell homeostasis and the IL-7/IL7R axis. Progressive infection results in loss of CD127+132- and gains in CD127-132+ CD4+ and CD8+ T-cells. We investigated the correlates of loss of CD127 from the T-cell surface to understand mechanisms underlying this homeostatic dysregulation.<h4>Methods</h4>Peripheral and cord blood mononuclear cells (PBMCs; CBMC) from healthy volunteers and PBMC from patients with HIV infection were studied. CD127+132-, CD127+132+ and CD127-132+ T-cells were phenotyped by activation, differentiation, proliferation and survival markers. Cellular HIV-DNA content and signal-joint T-cell receptor excision circles (sjTRECs) were measured.<h4>Results</h4>CD127+132- T-cells were enriched for naïve cells while CD127-132+ T-cells were enriched for activated/terminally differentiated T-cells in CD4+ and CD8+ subsets in health and HIV infection. HIV was associated with increased proportions of activated/terminally differentiated CD127-132+ T-cells. In contrast to CD127+132- T-cells, CD127-132+ T-cells were Ki-67+Bcl-2(low) and contained increased levels of HIV-DNA. Naïve CD127+132- T-cells contained a higher proportion of sjTRECs.<h4>Conclusion</h4>The loss of CD127 from the T-cell surface in HIV infection is driven by activation of CD127+132- recent thymic emigrants into CD127-132+ activated/terminally differentiated cells. This process likely results in an irreversible loss of CD127 and permanent distortion of T-cell homeostasis. |
format |
article |
author |
Sarah C Sasson John J Zaunders Nabila Seddiki Michelle Bailey Kristin McBride Kersten K Koelsch Kate M Merlin Don E Smith David A Cooper Anthony D Kelleher |
author_facet |
Sarah C Sasson John J Zaunders Nabila Seddiki Michelle Bailey Kristin McBride Kersten K Koelsch Kate M Merlin Don E Smith David A Cooper Anthony D Kelleher |
author_sort |
Sarah C Sasson |
title |
Progressive activation of CD127+132- recent thymic emigrants into terminally differentiated CD127-132+ T-cells in HIV-1 infection. |
title_short |
Progressive activation of CD127+132- recent thymic emigrants into terminally differentiated CD127-132+ T-cells in HIV-1 infection. |
title_full |
Progressive activation of CD127+132- recent thymic emigrants into terminally differentiated CD127-132+ T-cells in HIV-1 infection. |
title_fullStr |
Progressive activation of CD127+132- recent thymic emigrants into terminally differentiated CD127-132+ T-cells in HIV-1 infection. |
title_full_unstemmed |
Progressive activation of CD127+132- recent thymic emigrants into terminally differentiated CD127-132+ T-cells in HIV-1 infection. |
title_sort |
progressive activation of cd127+132- recent thymic emigrants into terminally differentiated cd127-132+ t-cells in hiv-1 infection. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2012 |
url |
https://doaj.org/article/82ee42fdf8e24afc9cd709cad2d3c664 |
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