HCV Specific IL-21 Producing T Cells but Not IL-17A Producing T Cells Are Associated with HCV Viral Control in HIV/HCV Coinfection
BACKGROUND: Decreased hepatitis C virus (HCV) clearance, faster cirrhosis progression and higher HCV RNA levels are associated with Human Immunodeficiency virus (HIV) coinfection. The CD4(+) T helper cytokines interleukin (IL)-21 and IL-17A are associated with virus control and inflammation, respect...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4849786/ https://www.ncbi.nlm.nih.gov/pubmed/27124305 http://dx.doi.org/10.1371/journal.pone.0154433 |
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author | MacParland, Sonya A. Fadel, Saleh M. Mihajlovic, Vesna Fawaz, Ali Kim, Connie Rahman, A. K. M. Nur-ur Liu, Jun Kaul, Rupert Kovacs, Colin Grebely, Jason Dore, Gregory J. Wong, David K. Ostrowski, Mario A. |
author_facet | MacParland, Sonya A. Fadel, Saleh M. Mihajlovic, Vesna Fawaz, Ali Kim, Connie Rahman, A. K. M. Nur-ur Liu, Jun Kaul, Rupert Kovacs, Colin Grebely, Jason Dore, Gregory J. Wong, David K. Ostrowski, Mario A. |
author_sort | MacParland, Sonya A. |
collection | PubMed |
description | BACKGROUND: Decreased hepatitis C virus (HCV) clearance, faster cirrhosis progression and higher HCV RNA levels are associated with Human Immunodeficiency virus (HIV) coinfection. The CD4(+) T helper cytokines interleukin (IL)-21 and IL-17A are associated with virus control and inflammation, respectively, both important in HCV and HIV disease progression. Here, we examined how antigen-specific production of these cytokines during HCV mono and HIV/HCV coinfection was associated with HCV virus control. METHODS: We measured HCV-specific IL-21 and IL-17A production by transwell cytokine secretion assay in PBMCs from monoinfected and coinfected individuals. Viral control was determined by plasma HCV RNA levels. RESULTS: In acutely infected individuals, those able to establish transient/complete HCV viral control tended to have stronger HCV-specific IL-21-production than non-controllers. HCV-specific IL-21 production also correlated with HCV viral decline in acute infection. Significantly stronger HCV-specific IL-21 production was detected in HAART-treated coinfected individuals. HCV-specific IL-17A production was not associated with lower plasma HCV RNA levels in acute or chronic HCV infection and responses were stronger in HIV coinfection. HCV-specific IL-21/ IL-17A responses did not correlate with microbial translocation or fibrosis. Exogenous IL-21 treatment of HCV-specific CD8(+) T cells from monoinfected individuals enhanced their function although CD8(+) T cells from coinfected individuals were somewhat refractory to the effects of IL-21. CONCLUSIONS: These data show that HCV-specific IL-21 and IL-17A-producing T cells are induced in HIV/HCV coinfection. In early HIV/HCV coinfection, IL-21 may contribute to viral control, and may represent a novel tool to enhance acute HCV clearance in HIV/HCV coinfected individuals. |
format | Online Article Text |
id | pubmed-4849786 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-48497862016-05-07 HCV Specific IL-21 Producing T Cells but Not IL-17A Producing T Cells Are Associated with HCV Viral Control in HIV/HCV Coinfection MacParland, Sonya A. Fadel, Saleh M. Mihajlovic, Vesna Fawaz, Ali Kim, Connie Rahman, A. K. M. Nur-ur Liu, Jun Kaul, Rupert Kovacs, Colin Grebely, Jason Dore, Gregory J. Wong, David K. Ostrowski, Mario A. PLoS One Research Article BACKGROUND: Decreased hepatitis C virus (HCV) clearance, faster cirrhosis progression and higher HCV RNA levels are associated with Human Immunodeficiency virus (HIV) coinfection. The CD4(+) T helper cytokines interleukin (IL)-21 and IL-17A are associated with virus control and inflammation, respectively, both important in HCV and HIV disease progression. Here, we examined how antigen-specific production of these cytokines during HCV mono and HIV/HCV coinfection was associated with HCV virus control. METHODS: We measured HCV-specific IL-21 and IL-17A production by transwell cytokine secretion assay in PBMCs from monoinfected and coinfected individuals. Viral control was determined by plasma HCV RNA levels. RESULTS: In acutely infected individuals, those able to establish transient/complete HCV viral control tended to have stronger HCV-specific IL-21-production than non-controllers. HCV-specific IL-21 production also correlated with HCV viral decline in acute infection. Significantly stronger HCV-specific IL-21 production was detected in HAART-treated coinfected individuals. HCV-specific IL-17A production was not associated with lower plasma HCV RNA levels in acute or chronic HCV infection and responses were stronger in HIV coinfection. HCV-specific IL-21/ IL-17A responses did not correlate with microbial translocation or fibrosis. Exogenous IL-21 treatment of HCV-specific CD8(+) T cells from monoinfected individuals enhanced their function although CD8(+) T cells from coinfected individuals were somewhat refractory to the effects of IL-21. CONCLUSIONS: These data show that HCV-specific IL-21 and IL-17A-producing T cells are induced in HIV/HCV coinfection. In early HIV/HCV coinfection, IL-21 may contribute to viral control, and may represent a novel tool to enhance acute HCV clearance in HIV/HCV coinfected individuals. Public Library of Science 2016-04-28 /pmc/articles/PMC4849786/ /pubmed/27124305 http://dx.doi.org/10.1371/journal.pone.0154433 Text en © 2016 MacParland 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 MacParland, Sonya A. Fadel, Saleh M. Mihajlovic, Vesna Fawaz, Ali Kim, Connie Rahman, A. K. M. Nur-ur Liu, Jun Kaul, Rupert Kovacs, Colin Grebely, Jason Dore, Gregory J. Wong, David K. Ostrowski, Mario A. HCV Specific IL-21 Producing T Cells but Not IL-17A Producing T Cells Are Associated with HCV Viral Control in HIV/HCV Coinfection |
title | HCV Specific IL-21 Producing T Cells but Not IL-17A Producing T Cells Are Associated with HCV Viral Control in HIV/HCV Coinfection |
title_full | HCV Specific IL-21 Producing T Cells but Not IL-17A Producing T Cells Are Associated with HCV Viral Control in HIV/HCV Coinfection |
title_fullStr | HCV Specific IL-21 Producing T Cells but Not IL-17A Producing T Cells Are Associated with HCV Viral Control in HIV/HCV Coinfection |
title_full_unstemmed | HCV Specific IL-21 Producing T Cells but Not IL-17A Producing T Cells Are Associated with HCV Viral Control in HIV/HCV Coinfection |
title_short | HCV Specific IL-21 Producing T Cells but Not IL-17A Producing T Cells Are Associated with HCV Viral Control in HIV/HCV Coinfection |
title_sort | hcv specific il-21 producing t cells but not il-17a producing t cells are associated with hcv viral control in hiv/hcv coinfection |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4849786/ https://www.ncbi.nlm.nih.gov/pubmed/27124305 http://dx.doi.org/10.1371/journal.pone.0154433 |
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