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Class-modeling analysis reveals T-cell homeostasis disturbances involved in loss of immune control in elite controllers
BACKGROUND: Despite long-lasting HIV replication control, a significant proportion of elite controller (EC) patients may experience CD4 T-cell loss. Discovering perturbations in immunological parameters could help our understanding of the mechanisms that may be operating in those patients experienci...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830067/ https://www.ncbi.nlm.nih.gov/pubmed/29490663 http://dx.doi.org/10.1186/s12916-018-1026-6 |
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author | Benito, José M. Ortiz, María C. León, Agathe Sarabia, Luis A. Ligos, José M. Montoya, María Garcia, Marcial Ruiz-Mateos, Ezequiel Palacios, Rosario Cabello, Alfonso Restrepo, Clara Rodriguez, Carmen del Romero, Jorge Leal, Manuel Muñoz-Fernández, María A. Alcamí, José García, Felipe Górgolas, Miguel Rallón, Norma |
author_facet | Benito, José M. Ortiz, María C. León, Agathe Sarabia, Luis A. Ligos, José M. Montoya, María Garcia, Marcial Ruiz-Mateos, Ezequiel Palacios, Rosario Cabello, Alfonso Restrepo, Clara Rodriguez, Carmen del Romero, Jorge Leal, Manuel Muñoz-Fernández, María A. Alcamí, José García, Felipe Górgolas, Miguel Rallón, Norma |
author_sort | Benito, José M. |
collection | PubMed |
description | BACKGROUND: Despite long-lasting HIV replication control, a significant proportion of elite controller (EC) patients may experience CD4 T-cell loss. Discovering perturbations in immunological parameters could help our understanding of the mechanisms that may be operating in those patients experiencing loss of immunological control. METHODS: A case–control study was performed to evaluate if alterations in different T-cell homeostatic parameters can predict CD4 T-cell loss in ECs by comparing data from EC patients showing significant CD4 decline (cases) and EC patients showing stable CD4 counts (controls). The partial least-squares–class modeling (PLS-CM) statistical methodology was employed to discriminate between the two groups of patients, and as a predictive model. RESULTS: Herein, we show that among T-cell homeostatic alterations, lower levels of naïve and recent thymic emigrant subsets of CD8 cells and higher levels of effector and senescent subsets of CD8 cells as well as higher levels of exhaustion of CD4 cells, measured prior to CD4 T-cell loss, predict the loss of immunological control. CONCLUSIONS: These data indicate that the parameters of T-cell homeostasis may identify those EC patients with a higher proclivity to CD4 T-cell loss. Our results may open new avenues for understanding the mechanisms underlying immunological progression despite HIV replication control, and eventually, for finding a functional cure through immune-based clinical trials. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12916-018-1026-6) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5830067 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-58300672018-03-05 Class-modeling analysis reveals T-cell homeostasis disturbances involved in loss of immune control in elite controllers Benito, José M. Ortiz, María C. León, Agathe Sarabia, Luis A. Ligos, José M. Montoya, María Garcia, Marcial Ruiz-Mateos, Ezequiel Palacios, Rosario Cabello, Alfonso Restrepo, Clara Rodriguez, Carmen del Romero, Jorge Leal, Manuel Muñoz-Fernández, María A. Alcamí, José García, Felipe Górgolas, Miguel Rallón, Norma BMC Med Research Article BACKGROUND: Despite long-lasting HIV replication control, a significant proportion of elite controller (EC) patients may experience CD4 T-cell loss. Discovering perturbations in immunological parameters could help our understanding of the mechanisms that may be operating in those patients experiencing loss of immunological control. METHODS: A case–control study was performed to evaluate if alterations in different T-cell homeostatic parameters can predict CD4 T-cell loss in ECs by comparing data from EC patients showing significant CD4 decline (cases) and EC patients showing stable CD4 counts (controls). The partial least-squares–class modeling (PLS-CM) statistical methodology was employed to discriminate between the two groups of patients, and as a predictive model. RESULTS: Herein, we show that among T-cell homeostatic alterations, lower levels of naïve and recent thymic emigrant subsets of CD8 cells and higher levels of effector and senescent subsets of CD8 cells as well as higher levels of exhaustion of CD4 cells, measured prior to CD4 T-cell loss, predict the loss of immunological control. CONCLUSIONS: These data indicate that the parameters of T-cell homeostasis may identify those EC patients with a higher proclivity to CD4 T-cell loss. Our results may open new avenues for understanding the mechanisms underlying immunological progression despite HIV replication control, and eventually, for finding a functional cure through immune-based clinical trials. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12916-018-1026-6) contains supplementary material, which is available to authorized users. BioMed Central 2018-02-28 /pmc/articles/PMC5830067/ /pubmed/29490663 http://dx.doi.org/10.1186/s12916-018-1026-6 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Benito, José M. Ortiz, María C. León, Agathe Sarabia, Luis A. Ligos, José M. Montoya, María Garcia, Marcial Ruiz-Mateos, Ezequiel Palacios, Rosario Cabello, Alfonso Restrepo, Clara Rodriguez, Carmen del Romero, Jorge Leal, Manuel Muñoz-Fernández, María A. Alcamí, José García, Felipe Górgolas, Miguel Rallón, Norma Class-modeling analysis reveals T-cell homeostasis disturbances involved in loss of immune control in elite controllers |
title | Class-modeling analysis reveals T-cell homeostasis disturbances involved in loss of immune control in elite controllers |
title_full | Class-modeling analysis reveals T-cell homeostasis disturbances involved in loss of immune control in elite controllers |
title_fullStr | Class-modeling analysis reveals T-cell homeostasis disturbances involved in loss of immune control in elite controllers |
title_full_unstemmed | Class-modeling analysis reveals T-cell homeostasis disturbances involved in loss of immune control in elite controllers |
title_short | Class-modeling analysis reveals T-cell homeostasis disturbances involved in loss of immune control in elite controllers |
title_sort | class-modeling analysis reveals t-cell homeostasis disturbances involved in loss of immune control in elite controllers |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830067/ https://www.ncbi.nlm.nih.gov/pubmed/29490663 http://dx.doi.org/10.1186/s12916-018-1026-6 |
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