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Expression of PD-1 and Tim-3 markers of T-cell exhaustion is associated with CD4 dynamics during the course of untreated and treated HIV infection

INTRODUCTION: T-cell exhaustion has been involved in the pathogenesis of HIV infection. We have longitudinally analyzed PD1 and Tim3 surrogate markers of T-cells exhaustion, in parallel with other markers of HIV progression, and its potential association with CD4 changes in treated and untreated inf...

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Autores principales: Rallón, Norma, García, Marcial, García-Samaniego, Javier, Cabello, Alfonso, Álvarez, Beatriz, Restrepo, Clara, Nistal, Sara, Górgolas, Miguel, Benito, José M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5843247/
https://www.ncbi.nlm.nih.gov/pubmed/29518102
http://dx.doi.org/10.1371/journal.pone.0193829
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author Rallón, Norma
García, Marcial
García-Samaniego, Javier
Cabello, Alfonso
Álvarez, Beatriz
Restrepo, Clara
Nistal, Sara
Górgolas, Miguel
Benito, José M.
author_facet Rallón, Norma
García, Marcial
García-Samaniego, Javier
Cabello, Alfonso
Álvarez, Beatriz
Restrepo, Clara
Nistal, Sara
Górgolas, Miguel
Benito, José M.
author_sort Rallón, Norma
collection PubMed
description INTRODUCTION: T-cell exhaustion has been involved in the pathogenesis of HIV infection. We have longitudinally analyzed PD1 and Tim3 surrogate markers of T-cells exhaustion, in parallel with other markers of HIV progression, and its potential association with CD4 changes in treated and untreated infection. PATIENTS AND METHODS: 96 HIV patients, 49 of them followed in the absence of cART (cART-naïve group) and 47 after initiation of cART (cART group) were included and followed for a median of 43 [IQR: 31–60] months. PD1 and Tim3 expression, CD8 T-cells activation, recent thymic emigrants, activation/apoptosis and turnover of CD4 cells were assessed at baseline and during follow up. Univariate and multivariate associations with CD4 evolution were explored. RESULTS: Parameters significantly associated with CD4 depletion in cART-naïve group were: baseline level (p = 0.02) and variation (p = 0.002) of PD1 and Tim3 co-expression on CD8, and variation of CD95 expression on CD4 (p = 0.007). Parameters significantly associated with CD4 restoration in cART group were: baseline level of CD38+HLADR- subset of CD8 (p = 0.01), variation of PD1 expression on CD8 (p = 0.036), variation of Tim3 expression on CD4 (p = 0.039) and variation of CD95 expression on CD4 (p = 0.035). CONCLUSIONS: Our results suggest that PD1 and Tim3 markers of exhaustion have a pivotal role in CD4 dynamics in HIV patients and its down-regulation would be a desirable effect of immunotherapies aimed to restore CD4 T-cell pool during progression of HIV infection.
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spelling pubmed-58432472018-03-23 Expression of PD-1 and Tim-3 markers of T-cell exhaustion is associated with CD4 dynamics during the course of untreated and treated HIV infection Rallón, Norma García, Marcial García-Samaniego, Javier Cabello, Alfonso Álvarez, Beatriz Restrepo, Clara Nistal, Sara Górgolas, Miguel Benito, José M. PLoS One Research Article INTRODUCTION: T-cell exhaustion has been involved in the pathogenesis of HIV infection. We have longitudinally analyzed PD1 and Tim3 surrogate markers of T-cells exhaustion, in parallel with other markers of HIV progression, and its potential association with CD4 changes in treated and untreated infection. PATIENTS AND METHODS: 96 HIV patients, 49 of them followed in the absence of cART (cART-naïve group) and 47 after initiation of cART (cART group) were included and followed for a median of 43 [IQR: 31–60] months. PD1 and Tim3 expression, CD8 T-cells activation, recent thymic emigrants, activation/apoptosis and turnover of CD4 cells were assessed at baseline and during follow up. Univariate and multivariate associations with CD4 evolution were explored. RESULTS: Parameters significantly associated with CD4 depletion in cART-naïve group were: baseline level (p = 0.02) and variation (p = 0.002) of PD1 and Tim3 co-expression on CD8, and variation of CD95 expression on CD4 (p = 0.007). Parameters significantly associated with CD4 restoration in cART group were: baseline level of CD38+HLADR- subset of CD8 (p = 0.01), variation of PD1 expression on CD8 (p = 0.036), variation of Tim3 expression on CD4 (p = 0.039) and variation of CD95 expression on CD4 (p = 0.035). CONCLUSIONS: Our results suggest that PD1 and Tim3 markers of exhaustion have a pivotal role in CD4 dynamics in HIV patients and its down-regulation would be a desirable effect of immunotherapies aimed to restore CD4 T-cell pool during progression of HIV infection. Public Library of Science 2018-03-08 /pmc/articles/PMC5843247/ /pubmed/29518102 http://dx.doi.org/10.1371/journal.pone.0193829 Text en © 2018 Rallón 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Rallón, Norma
García, Marcial
García-Samaniego, Javier
Cabello, Alfonso
Álvarez, Beatriz
Restrepo, Clara
Nistal, Sara
Górgolas, Miguel
Benito, José M.
Expression of PD-1 and Tim-3 markers of T-cell exhaustion is associated with CD4 dynamics during the course of untreated and treated HIV infection
title Expression of PD-1 and Tim-3 markers of T-cell exhaustion is associated with CD4 dynamics during the course of untreated and treated HIV infection
title_full Expression of PD-1 and Tim-3 markers of T-cell exhaustion is associated with CD4 dynamics during the course of untreated and treated HIV infection
title_fullStr Expression of PD-1 and Tim-3 markers of T-cell exhaustion is associated with CD4 dynamics during the course of untreated and treated HIV infection
title_full_unstemmed Expression of PD-1 and Tim-3 markers of T-cell exhaustion is associated with CD4 dynamics during the course of untreated and treated HIV infection
title_short Expression of PD-1 and Tim-3 markers of T-cell exhaustion is associated with CD4 dynamics during the course of untreated and treated HIV infection
title_sort expression of pd-1 and tim-3 markers of t-cell exhaustion is associated with cd4 dynamics during the course of untreated and treated hiv infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5843247/
https://www.ncbi.nlm.nih.gov/pubmed/29518102
http://dx.doi.org/10.1371/journal.pone.0193829
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