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Relationships between IL-17(+) Subsets, Tregs and pDCs That Distinguish among SIV Infected Elite Controllers, Low, Medium and High Viral Load Rhesus Macaques
Comprehensive studies of the frequencies and absolute numbers of the various cell lineages that synthesize IL-17 in the blood and corresponding gastrointestinal (GI) tissues, their correlation with CD4(+) Tregs, CD8(+) Tregs, total and IFN-α synthesizing plasmacytoid dendritic cells (pDC) relative t...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3631185/ https://www.ncbi.nlm.nih.gov/pubmed/23620737 http://dx.doi.org/10.1371/journal.pone.0061264 |
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author | Khowawisetsut, Ladawan Pattanapanyasat, Kovit Onlamoon, Nattawat Mayne, Ann E. Little, Dawn M. Villinger, Francois Ansari, Aftab A. |
author_facet | Khowawisetsut, Ladawan Pattanapanyasat, Kovit Onlamoon, Nattawat Mayne, Ann E. Little, Dawn M. Villinger, Francois Ansari, Aftab A. |
author_sort | Khowawisetsut, Ladawan |
collection | PubMed |
description | Comprehensive studies of the frequencies and absolute numbers of the various cell lineages that synthesize IL-17 in the blood and corresponding gastrointestinal (GI) tissues, their correlation with CD4(+) Tregs, CD8(+) Tregs, total and IFN-α synthesizing plasmacytoid dendritic cells (pDC) relative to plasma viral load in SIV infection has been lacking. The unique availability of SIV infected rhesus macaques (RM) classified as Elite Controllers (EC), and those with Low, Intermediate and High Viral Loads (HVL) provided a unique opportunity to address this issue. Results of these studies showed that EC demonstrated a remarkable ability to reverse changes that are induced acutely by SIV in the various cell lineages. Highlights of the differences between EC and HVL RM within Gastro-intestinal tissues (GIT) was the maintenance and/or increases in the levels of IL-17 synthesizing CD4, CD8, and NK cells and pDCs associated with slight decreases in the levels of CD4(+) Tregs and IFN-α synthesizing pDCs in EC as compared with decreases in the levels of IL-17 synthesizing CD4, CD8 and NK cells associated with increases in pDCs and IFN-α synthesizing pDCs in HVL monkeys. A previously underappreciated role for CD8(+) Tregs was also noted with a moderate increase in ECs but further increases of CD8(+) Tregs with increasing VL in viremic monkeys. Positive correlations between plasma VL and decreases in the levels of Th17, Tc17, NK-17, CD4(+) Tregs and increases in the levels of CD8(+) Tregs, total and IFN-α synthesizing pDCs were also noted. This study also identified 2 additional IL-17(+) subsets in GIT as CD3(−/)CD8(+)/NKG2a(−) and CD3(+)/CD8(+)/NKG2a(+) subsets. Studies also suggest a limited role for IFN-α synthesizing pDCs in chronic immune activation despite persistent up-regulation of ISGs. Finally, elevated persistent innate immune responses appear associated with poor prognosis. These findings provide an initial foundation for markers important to follow for vaccine design. |
format | Online Article Text |
id | pubmed-3631185 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-36311852013-04-25 Relationships between IL-17(+) Subsets, Tregs and pDCs That Distinguish among SIV Infected Elite Controllers, Low, Medium and High Viral Load Rhesus Macaques Khowawisetsut, Ladawan Pattanapanyasat, Kovit Onlamoon, Nattawat Mayne, Ann E. Little, Dawn M. Villinger, Francois Ansari, Aftab A. PLoS One Research Article Comprehensive studies of the frequencies and absolute numbers of the various cell lineages that synthesize IL-17 in the blood and corresponding gastrointestinal (GI) tissues, their correlation with CD4(+) Tregs, CD8(+) Tregs, total and IFN-α synthesizing plasmacytoid dendritic cells (pDC) relative to plasma viral load in SIV infection has been lacking. The unique availability of SIV infected rhesus macaques (RM) classified as Elite Controllers (EC), and those with Low, Intermediate and High Viral Loads (HVL) provided a unique opportunity to address this issue. Results of these studies showed that EC demonstrated a remarkable ability to reverse changes that are induced acutely by SIV in the various cell lineages. Highlights of the differences between EC and HVL RM within Gastro-intestinal tissues (GIT) was the maintenance and/or increases in the levels of IL-17 synthesizing CD4, CD8, and NK cells and pDCs associated with slight decreases in the levels of CD4(+) Tregs and IFN-α synthesizing pDCs in EC as compared with decreases in the levels of IL-17 synthesizing CD4, CD8 and NK cells associated with increases in pDCs and IFN-α synthesizing pDCs in HVL monkeys. A previously underappreciated role for CD8(+) Tregs was also noted with a moderate increase in ECs but further increases of CD8(+) Tregs with increasing VL in viremic monkeys. Positive correlations between plasma VL and decreases in the levels of Th17, Tc17, NK-17, CD4(+) Tregs and increases in the levels of CD8(+) Tregs, total and IFN-α synthesizing pDCs were also noted. This study also identified 2 additional IL-17(+) subsets in GIT as CD3(−/)CD8(+)/NKG2a(−) and CD3(+)/CD8(+)/NKG2a(+) subsets. Studies also suggest a limited role for IFN-α synthesizing pDCs in chronic immune activation despite persistent up-regulation of ISGs. Finally, elevated persistent innate immune responses appear associated with poor prognosis. These findings provide an initial foundation for markers important to follow for vaccine design. Public Library of Science 2013-04-19 /pmc/articles/PMC3631185/ /pubmed/23620737 http://dx.doi.org/10.1371/journal.pone.0061264 Text en © 2013 Khowawisetsut 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Khowawisetsut, Ladawan Pattanapanyasat, Kovit Onlamoon, Nattawat Mayne, Ann E. Little, Dawn M. Villinger, Francois Ansari, Aftab A. Relationships between IL-17(+) Subsets, Tregs and pDCs That Distinguish among SIV Infected Elite Controllers, Low, Medium and High Viral Load Rhesus Macaques |
title | Relationships between IL-17(+) Subsets, Tregs and pDCs That Distinguish among SIV Infected Elite Controllers, Low, Medium and High Viral Load Rhesus Macaques |
title_full | Relationships between IL-17(+) Subsets, Tregs and pDCs That Distinguish among SIV Infected Elite Controllers, Low, Medium and High Viral Load Rhesus Macaques |
title_fullStr | Relationships between IL-17(+) Subsets, Tregs and pDCs That Distinguish among SIV Infected Elite Controllers, Low, Medium and High Viral Load Rhesus Macaques |
title_full_unstemmed | Relationships between IL-17(+) Subsets, Tregs and pDCs That Distinguish among SIV Infected Elite Controllers, Low, Medium and High Viral Load Rhesus Macaques |
title_short | Relationships between IL-17(+) Subsets, Tregs and pDCs That Distinguish among SIV Infected Elite Controllers, Low, Medium and High Viral Load Rhesus Macaques |
title_sort | relationships between il-17(+) subsets, tregs and pdcs that distinguish among siv infected elite controllers, low, medium and high viral load rhesus macaques |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3631185/ https://www.ncbi.nlm.nih.gov/pubmed/23620737 http://dx.doi.org/10.1371/journal.pone.0061264 |
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