Cargando…
Longitudinal Analysis of Peripheral and Colonic CD161(+) CD4(+) T Cell Dysfunction in Acute HIV-1 Infection and Effects of Early Treatment Initiation
CD161 expression on CD4(+) T cells is associated with a Th17 functional phenotype, as well as with an innate capacity to respond to interleukin (IL)-12 and IL-18 without T cell receptor (TCR) stimulation. Chronic HIV-1 infection is associated with loss of the CD161(+) CD4 T cell population, and non-...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764746/ https://www.ncbi.nlm.nih.gov/pubmed/33322496 http://dx.doi.org/10.3390/v12121426 |
_version_ | 1783628329876717568 |
---|---|
author | Lal, Kerri G. Phuang-Ngern, Yuwadee Suhkumvittaya, Suchada Leeansyah, Edwin Alrubayyi, Aljawharah Dias, Joana Waickman, Adam Kim, Dohoon Kroon, Eugène Pinyakorn, Suteeraporn Eller, Leigh Anne Maciel Jr., Milton Rerknimitr, Rungsun Chomchey, Nitiya Phanuphak, Nittaya de Souza, Mark S. Nitayaphan, Sorachai Ake, Julie A. Vasan, Sandhya Robb, Merlin L. Ananworanich, Jintanat Sandberg, Johan K. Schuetz, Alexandra Eller, Michael A. Paquin-Proulx, Dominic |
author_facet | Lal, Kerri G. Phuang-Ngern, Yuwadee Suhkumvittaya, Suchada Leeansyah, Edwin Alrubayyi, Aljawharah Dias, Joana Waickman, Adam Kim, Dohoon Kroon, Eugène Pinyakorn, Suteeraporn Eller, Leigh Anne Maciel Jr., Milton Rerknimitr, Rungsun Chomchey, Nitiya Phanuphak, Nittaya de Souza, Mark S. Nitayaphan, Sorachai Ake, Julie A. Vasan, Sandhya Robb, Merlin L. Ananworanich, Jintanat Sandberg, Johan K. Schuetz, Alexandra Eller, Michael A. Paquin-Proulx, Dominic |
author_sort | Lal, Kerri G. |
collection | PubMed |
description | CD161 expression on CD4(+) T cells is associated with a Th17 functional phenotype, as well as with an innate capacity to respond to interleukin (IL)-12 and IL-18 without T cell receptor (TCR) stimulation. Chronic HIV-1 infection is associated with loss of the CD161(+) CD4 T cell population, and non-human primate studies suggest that their depletion is associated with disease progression. However, the dynamics of the CD161(+) CD4(+) T cell population during acute HIV-1 infection remains unknown. In this study, we characterize peripheral blood CD161(+) CD4(+) T cells in detail, and examine how they are affected during the earliest stages of HIV-1 infection. Unbiased surface proteome screening and principal component analysis indicated that CD161(+) CD4(+) T cells are relatively phenotypically homogeneous between donors, and are intermediates between conventional CD4 T cells and innate-like T cells. In acute untreated HIV-1 infection, the circulating CD161(+) CD4(+) T cell population decreased in frequency, as did absolute cell counts starting from peak viral load, with elevated levels of activation and exhaustion markers expressed throughout acute HIV-1 infection. The capacity of these cells to respond to stimulation with IL-12 and IL-18 was also reduced. Early initiation of anti-retroviral treatment (ART) during acute HIV-1 infection restored the functionality of peripheral blood CD161(+) CD4(+) T cells, but not their frequency. In contrast, early ART initiation prevented the decline of colonic CD161(+) CD4(+) T cells that otherwise started during acute infection. Furthermore, loss of peripheral and colonic CD161(+) CD4(+) T cells in untreated infection was associated with levels of viral load. These results suggest that acute HIV-1 infection has profound effects on the CD161(+) CD4(+) T cell population that could not be completely prevented by the initiation of ART. |
format | Online Article Text |
id | pubmed-7764746 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-77647462020-12-27 Longitudinal Analysis of Peripheral and Colonic CD161(+) CD4(+) T Cell Dysfunction in Acute HIV-1 Infection and Effects of Early Treatment Initiation Lal, Kerri G. Phuang-Ngern, Yuwadee Suhkumvittaya, Suchada Leeansyah, Edwin Alrubayyi, Aljawharah Dias, Joana Waickman, Adam Kim, Dohoon Kroon, Eugène Pinyakorn, Suteeraporn Eller, Leigh Anne Maciel Jr., Milton Rerknimitr, Rungsun Chomchey, Nitiya Phanuphak, Nittaya de Souza, Mark S. Nitayaphan, Sorachai Ake, Julie A. Vasan, Sandhya Robb, Merlin L. Ananworanich, Jintanat Sandberg, Johan K. Schuetz, Alexandra Eller, Michael A. Paquin-Proulx, Dominic Viruses Article CD161 expression on CD4(+) T cells is associated with a Th17 functional phenotype, as well as with an innate capacity to respond to interleukin (IL)-12 and IL-18 without T cell receptor (TCR) stimulation. Chronic HIV-1 infection is associated with loss of the CD161(+) CD4 T cell population, and non-human primate studies suggest that their depletion is associated with disease progression. However, the dynamics of the CD161(+) CD4(+) T cell population during acute HIV-1 infection remains unknown. In this study, we characterize peripheral blood CD161(+) CD4(+) T cells in detail, and examine how they are affected during the earliest stages of HIV-1 infection. Unbiased surface proteome screening and principal component analysis indicated that CD161(+) CD4(+) T cells are relatively phenotypically homogeneous between donors, and are intermediates between conventional CD4 T cells and innate-like T cells. In acute untreated HIV-1 infection, the circulating CD161(+) CD4(+) T cell population decreased in frequency, as did absolute cell counts starting from peak viral load, with elevated levels of activation and exhaustion markers expressed throughout acute HIV-1 infection. The capacity of these cells to respond to stimulation with IL-12 and IL-18 was also reduced. Early initiation of anti-retroviral treatment (ART) during acute HIV-1 infection restored the functionality of peripheral blood CD161(+) CD4(+) T cells, but not their frequency. In contrast, early ART initiation prevented the decline of colonic CD161(+) CD4(+) T cells that otherwise started during acute infection. Furthermore, loss of peripheral and colonic CD161(+) CD4(+) T cells in untreated infection was associated with levels of viral load. These results suggest that acute HIV-1 infection has profound effects on the CD161(+) CD4(+) T cell population that could not be completely prevented by the initiation of ART. MDPI 2020-12-11 /pmc/articles/PMC7764746/ /pubmed/33322496 http://dx.doi.org/10.3390/v12121426 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Lal, Kerri G. Phuang-Ngern, Yuwadee Suhkumvittaya, Suchada Leeansyah, Edwin Alrubayyi, Aljawharah Dias, Joana Waickman, Adam Kim, Dohoon Kroon, Eugène Pinyakorn, Suteeraporn Eller, Leigh Anne Maciel Jr., Milton Rerknimitr, Rungsun Chomchey, Nitiya Phanuphak, Nittaya de Souza, Mark S. Nitayaphan, Sorachai Ake, Julie A. Vasan, Sandhya Robb, Merlin L. Ananworanich, Jintanat Sandberg, Johan K. Schuetz, Alexandra Eller, Michael A. Paquin-Proulx, Dominic Longitudinal Analysis of Peripheral and Colonic CD161(+) CD4(+) T Cell Dysfunction in Acute HIV-1 Infection and Effects of Early Treatment Initiation |
title | Longitudinal Analysis of Peripheral and Colonic CD161(+) CD4(+) T Cell Dysfunction in Acute HIV-1 Infection and Effects of Early Treatment Initiation |
title_full | Longitudinal Analysis of Peripheral and Colonic CD161(+) CD4(+) T Cell Dysfunction in Acute HIV-1 Infection and Effects of Early Treatment Initiation |
title_fullStr | Longitudinal Analysis of Peripheral and Colonic CD161(+) CD4(+) T Cell Dysfunction in Acute HIV-1 Infection and Effects of Early Treatment Initiation |
title_full_unstemmed | Longitudinal Analysis of Peripheral and Colonic CD161(+) CD4(+) T Cell Dysfunction in Acute HIV-1 Infection and Effects of Early Treatment Initiation |
title_short | Longitudinal Analysis of Peripheral and Colonic CD161(+) CD4(+) T Cell Dysfunction in Acute HIV-1 Infection and Effects of Early Treatment Initiation |
title_sort | longitudinal analysis of peripheral and colonic cd161(+) cd4(+) t cell dysfunction in acute hiv-1 infection and effects of early treatment initiation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764746/ https://www.ncbi.nlm.nih.gov/pubmed/33322496 http://dx.doi.org/10.3390/v12121426 |
work_keys_str_mv | AT lalkerrig longitudinalanalysisofperipheralandcoloniccd161cd4tcelldysfunctioninacutehiv1infectionandeffectsofearlytreatmentinitiation AT phuangngernyuwadee longitudinalanalysisofperipheralandcoloniccd161cd4tcelldysfunctioninacutehiv1infectionandeffectsofearlytreatmentinitiation AT suhkumvittayasuchada longitudinalanalysisofperipheralandcoloniccd161cd4tcelldysfunctioninacutehiv1infectionandeffectsofearlytreatmentinitiation AT leeansyahedwin longitudinalanalysisofperipheralandcoloniccd161cd4tcelldysfunctioninacutehiv1infectionandeffectsofearlytreatmentinitiation AT alrubayyialjawharah longitudinalanalysisofperipheralandcoloniccd161cd4tcelldysfunctioninacutehiv1infectionandeffectsofearlytreatmentinitiation AT diasjoana longitudinalanalysisofperipheralandcoloniccd161cd4tcelldysfunctioninacutehiv1infectionandeffectsofearlytreatmentinitiation AT waickmanadam longitudinalanalysisofperipheralandcoloniccd161cd4tcelldysfunctioninacutehiv1infectionandeffectsofearlytreatmentinitiation AT kimdohoon longitudinalanalysisofperipheralandcoloniccd161cd4tcelldysfunctioninacutehiv1infectionandeffectsofearlytreatmentinitiation AT krooneugene longitudinalanalysisofperipheralandcoloniccd161cd4tcelldysfunctioninacutehiv1infectionandeffectsofearlytreatmentinitiation AT pinyakornsuteeraporn longitudinalanalysisofperipheralandcoloniccd161cd4tcelldysfunctioninacutehiv1infectionandeffectsofearlytreatmentinitiation AT ellerleighanne longitudinalanalysisofperipheralandcoloniccd161cd4tcelldysfunctioninacutehiv1infectionandeffectsofearlytreatmentinitiation AT macieljrmilton longitudinalanalysisofperipheralandcoloniccd161cd4tcelldysfunctioninacutehiv1infectionandeffectsofearlytreatmentinitiation AT rerknimitrrungsun longitudinalanalysisofperipheralandcoloniccd161cd4tcelldysfunctioninacutehiv1infectionandeffectsofearlytreatmentinitiation AT chomcheynitiya longitudinalanalysisofperipheralandcoloniccd161cd4tcelldysfunctioninacutehiv1infectionandeffectsofearlytreatmentinitiation AT phanuphaknittaya longitudinalanalysisofperipheralandcoloniccd161cd4tcelldysfunctioninacutehiv1infectionandeffectsofearlytreatmentinitiation AT desouzamarks longitudinalanalysisofperipheralandcoloniccd161cd4tcelldysfunctioninacutehiv1infectionandeffectsofearlytreatmentinitiation AT nitayaphansorachai longitudinalanalysisofperipheralandcoloniccd161cd4tcelldysfunctioninacutehiv1infectionandeffectsofearlytreatmentinitiation AT akejuliea longitudinalanalysisofperipheralandcoloniccd161cd4tcelldysfunctioninacutehiv1infectionandeffectsofearlytreatmentinitiation AT vasansandhya longitudinalanalysisofperipheralandcoloniccd161cd4tcelldysfunctioninacutehiv1infectionandeffectsofearlytreatmentinitiation AT robbmerlinl longitudinalanalysisofperipheralandcoloniccd161cd4tcelldysfunctioninacutehiv1infectionandeffectsofearlytreatmentinitiation AT ananworanichjintanat longitudinalanalysisofperipheralandcoloniccd161cd4tcelldysfunctioninacutehiv1infectionandeffectsofearlytreatmentinitiation AT sandbergjohank longitudinalanalysisofperipheralandcoloniccd161cd4tcelldysfunctioninacutehiv1infectionandeffectsofearlytreatmentinitiation AT schuetzalexandra longitudinalanalysisofperipheralandcoloniccd161cd4tcelldysfunctioninacutehiv1infectionandeffectsofearlytreatmentinitiation AT ellermichaela longitudinalanalysisofperipheralandcoloniccd161cd4tcelldysfunctioninacutehiv1infectionandeffectsofearlytreatmentinitiation AT paquinproulxdominic longitudinalanalysisofperipheralandcoloniccd161cd4tcelldysfunctioninacutehiv1infectionandeffectsofearlytreatmentinitiation AT longitudinalanalysisofperipheralandcoloniccd161cd4tcelldysfunctioninacutehiv1infectionandeffectsofearlytreatmentinitiation |