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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
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.
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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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