Noncytolytic CD8(+) Cell Mediated Antiviral Response Represents a Strong Element in the Immune Response of Simian Immunodeficiency Virus-Infected Long-Term Non-Progressing Rhesus Macaques

The ability of long term non progressors to maintain very low levels of HIV/SIV and a healthy state, involves various host genetic and immunological factors. CD8+ non-cytolytic antiviral response (CNAR) most likely plays an important role in this regard. In order to gain a deeper insight into this u...

Descripción completa

Detalles Bibliográficos
Autores principales: Javed, Aneela, Leuchte, Nicole, Neumann, Berit, Sopper, Sieghart, Sauermann, Ulrike
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4638345/
https://www.ncbi.nlm.nih.gov/pubmed/26551355
http://dx.doi.org/10.1371/journal.pone.0142086
_version_ 1782399901020192768
author Javed, Aneela
Leuchte, Nicole
Neumann, Berit
Sopper, Sieghart
Sauermann, Ulrike
author_facet Javed, Aneela
Leuchte, Nicole
Neumann, Berit
Sopper, Sieghart
Sauermann, Ulrike
author_sort Javed, Aneela
collection PubMed
description The ability of long term non progressors to maintain very low levels of HIV/SIV and a healthy state, involves various host genetic and immunological factors. CD8+ non-cytolytic antiviral response (CNAR) most likely plays an important role in this regard. In order to gain a deeper insight into this unique phenomenon, the ability of CD8+ T cells to suppress viral replication in vitro was investigated in 16 uninfected, longitudinally in 23 SIV-infected long-term non-progressing (LTNPs), and 10 SIV-infected rhesus macaques with progressing disease. An acute infection assay utilizing CD4(+) cells from MHC-mismatched monkeys to avoid cytolytic responses was employed. The study has identified CNAR as a long-term stable activity that inversely correlated with plasma viral load. The activity was also detected in CD8(+) cells of uninfected macaques, which indicates that CNAR is not necessarily a virus specific response but increases after SIV-infection. Physical contact between CD4(+) and CD8(+) cells was mainly involved in mediating viral inhibition. Loss of this activity appeared to be due to a loss of CNAR-expressing CD8+ cells as well as a reduction of CNAR-responsive CD4+ cells. In contrast, in vitro viral replication did not differ in CD4+ cells from un-infected macaques, CNAR(+) and CNAR(-) LTNPs. A role for transitional memory cells in supporting CNAR in the macaque model of AIDS was questionable. CNAR appears to represent an important part of the immune response displayed by CD8+ T cells which might be underestimated up to now.
format Online
Article
Text
id pubmed-4638345
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-46383452015-11-13 Noncytolytic CD8(+) Cell Mediated Antiviral Response Represents a Strong Element in the Immune Response of Simian Immunodeficiency Virus-Infected Long-Term Non-Progressing Rhesus Macaques Javed, Aneela Leuchte, Nicole Neumann, Berit Sopper, Sieghart Sauermann, Ulrike PLoS One Research Article The ability of long term non progressors to maintain very low levels of HIV/SIV and a healthy state, involves various host genetic and immunological factors. CD8+ non-cytolytic antiviral response (CNAR) most likely plays an important role in this regard. In order to gain a deeper insight into this unique phenomenon, the ability of CD8+ T cells to suppress viral replication in vitro was investigated in 16 uninfected, longitudinally in 23 SIV-infected long-term non-progressing (LTNPs), and 10 SIV-infected rhesus macaques with progressing disease. An acute infection assay utilizing CD4(+) cells from MHC-mismatched monkeys to avoid cytolytic responses was employed. The study has identified CNAR as a long-term stable activity that inversely correlated with plasma viral load. The activity was also detected in CD8(+) cells of uninfected macaques, which indicates that CNAR is not necessarily a virus specific response but increases after SIV-infection. Physical contact between CD4(+) and CD8(+) cells was mainly involved in mediating viral inhibition. Loss of this activity appeared to be due to a loss of CNAR-expressing CD8+ cells as well as a reduction of CNAR-responsive CD4+ cells. In contrast, in vitro viral replication did not differ in CD4+ cells from un-infected macaques, CNAR(+) and CNAR(-) LTNPs. A role for transitional memory cells in supporting CNAR in the macaque model of AIDS was questionable. CNAR appears to represent an important part of the immune response displayed by CD8+ T cells which might be underestimated up to now. Public Library of Science 2015-11-09 /pmc/articles/PMC4638345/ /pubmed/26551355 http://dx.doi.org/10.1371/journal.pone.0142086 Text en © 2015 Javed 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
Javed, Aneela
Leuchte, Nicole
Neumann, Berit
Sopper, Sieghart
Sauermann, Ulrike
Noncytolytic CD8(+) Cell Mediated Antiviral Response Represents a Strong Element in the Immune Response of Simian Immunodeficiency Virus-Infected Long-Term Non-Progressing Rhesus Macaques
title Noncytolytic CD8(+) Cell Mediated Antiviral Response Represents a Strong Element in the Immune Response of Simian Immunodeficiency Virus-Infected Long-Term Non-Progressing Rhesus Macaques
title_full Noncytolytic CD8(+) Cell Mediated Antiviral Response Represents a Strong Element in the Immune Response of Simian Immunodeficiency Virus-Infected Long-Term Non-Progressing Rhesus Macaques
title_fullStr Noncytolytic CD8(+) Cell Mediated Antiviral Response Represents a Strong Element in the Immune Response of Simian Immunodeficiency Virus-Infected Long-Term Non-Progressing Rhesus Macaques
title_full_unstemmed Noncytolytic CD8(+) Cell Mediated Antiviral Response Represents a Strong Element in the Immune Response of Simian Immunodeficiency Virus-Infected Long-Term Non-Progressing Rhesus Macaques
title_short Noncytolytic CD8(+) Cell Mediated Antiviral Response Represents a Strong Element in the Immune Response of Simian Immunodeficiency Virus-Infected Long-Term Non-Progressing Rhesus Macaques
title_sort noncytolytic cd8(+) cell mediated antiviral response represents a strong element in the immune response of simian immunodeficiency virus-infected long-term non-progressing rhesus macaques
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4638345/
https://www.ncbi.nlm.nih.gov/pubmed/26551355
http://dx.doi.org/10.1371/journal.pone.0142086
work_keys_str_mv AT javedaneela noncytolyticcd8cellmediatedantiviralresponserepresentsastrongelementintheimmuneresponseofsimianimmunodeficiencyvirusinfectedlongtermnonprogressingrhesusmacaques
AT leuchtenicole noncytolyticcd8cellmediatedantiviralresponserepresentsastrongelementintheimmuneresponseofsimianimmunodeficiencyvirusinfectedlongtermnonprogressingrhesusmacaques
AT neumannberit noncytolyticcd8cellmediatedantiviralresponserepresentsastrongelementintheimmuneresponseofsimianimmunodeficiencyvirusinfectedlongtermnonprogressingrhesusmacaques
AT soppersieghart noncytolyticcd8cellmediatedantiviralresponserepresentsastrongelementintheimmuneresponseofsimianimmunodeficiencyvirusinfectedlongtermnonprogressingrhesusmacaques
AT sauermannulrike noncytolyticcd8cellmediatedantiviralresponserepresentsastrongelementintheimmuneresponseofsimianimmunodeficiencyvirusinfectedlongtermnonprogressingrhesusmacaques