In vivo CD8+ T-cell suppression of siv viremia is not mediated by CTL clearance of productively infected cells.

The CD8+ T-cell is a key mediator of antiviral immunity, potentially contributing to control of pathogenic lentiviral infection through both innate and adaptive mechanisms. We studied viral dynamics during antiretroviral treatment of simian immunodeficiency virus (SIV) infected rhesus macaques follo...

Full description

Bibliographic Details
Main Authors: Joseph K Wong, Matthew C Strain, Rodin Porrata, Elizabeth Reay, Sumathi Sankaran-Walters, Caroline C Ignacio, Theresa Russell, Satish K Pillai, David J Looney, Satya Dandekar
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2010-01-01
Series:PLoS Pathogens
Online Access:http://europepmc.org/articles/PMC2813272?pdf=render
_version_ 1818021827107094528
author Joseph K Wong
Matthew C Strain
Rodin Porrata
Elizabeth Reay
Sumathi Sankaran-Walters
Caroline C Ignacio
Theresa Russell
Satish K Pillai
David J Looney
Satya Dandekar
author_facet Joseph K Wong
Matthew C Strain
Rodin Porrata
Elizabeth Reay
Sumathi Sankaran-Walters
Caroline C Ignacio
Theresa Russell
Satish K Pillai
David J Looney
Satya Dandekar
author_sort Joseph K Wong
collection DOAJ
description The CD8+ T-cell is a key mediator of antiviral immunity, potentially contributing to control of pathogenic lentiviral infection through both innate and adaptive mechanisms. We studied viral dynamics during antiretroviral treatment of simian immunodeficiency virus (SIV) infected rhesus macaques following CD8+ T-cell depletion to test the importance of adaptive cytotoxic effects in clearance of cells productively infected with SIV. As previously described, plasma viral load (VL) increased following CD8+ T-cell depletion and was proportional to the magnitude of CD8+ T-cell depletion in the GALT, confirming a direct relationship between CD8+ T-cell loss and viral replication. Surprisingly, first phase plasma virus decay following administration of antiretroviral drugs was not slower in CD8+ T-cell depleted animals compared with controls indicating that the short lifespan of the average productively infected cell is not a reflection of cytotoxic T-lymphocyte (CTL) killing. Our findings support a dominant role for non-cytotoxic effects of CD8+ T-cells on control of pathogenic lentiviral infection and suggest that cytotoxic effects, if present, are limited to early, pre-productive stages of the viral life cycle. These observations have important implications for future strategies to augment immune control of HIV.
first_indexed 2024-04-14T08:23:16Z
format Article
id doaj.art-8f2d11b947c149c189bf43c97caca181
institution Directory Open Access Journal
issn 1553-7366
1553-7374
language English
last_indexed 2024-04-14T08:23:16Z
publishDate 2010-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS Pathogens
spelling doaj.art-8f2d11b947c149c189bf43c97caca1812022-12-22T02:04:08ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742010-01-0161e100074810.1371/journal.ppat.1000748In vivo CD8+ T-cell suppression of siv viremia is not mediated by CTL clearance of productively infected cells.Joseph K WongMatthew C StrainRodin PorrataElizabeth ReaySumathi Sankaran-WaltersCaroline C IgnacioTheresa RussellSatish K PillaiDavid J LooneySatya DandekarThe CD8+ T-cell is a key mediator of antiviral immunity, potentially contributing to control of pathogenic lentiviral infection through both innate and adaptive mechanisms. We studied viral dynamics during antiretroviral treatment of simian immunodeficiency virus (SIV) infected rhesus macaques following CD8+ T-cell depletion to test the importance of adaptive cytotoxic effects in clearance of cells productively infected with SIV. As previously described, plasma viral load (VL) increased following CD8+ T-cell depletion and was proportional to the magnitude of CD8+ T-cell depletion in the GALT, confirming a direct relationship between CD8+ T-cell loss and viral replication. Surprisingly, first phase plasma virus decay following administration of antiretroviral drugs was not slower in CD8+ T-cell depleted animals compared with controls indicating that the short lifespan of the average productively infected cell is not a reflection of cytotoxic T-lymphocyte (CTL) killing. Our findings support a dominant role for non-cytotoxic effects of CD8+ T-cells on control of pathogenic lentiviral infection and suggest that cytotoxic effects, if present, are limited to early, pre-productive stages of the viral life cycle. These observations have important implications for future strategies to augment immune control of HIV.http://europepmc.org/articles/PMC2813272?pdf=render
spellingShingle Joseph K Wong
Matthew C Strain
Rodin Porrata
Elizabeth Reay
Sumathi Sankaran-Walters
Caroline C Ignacio
Theresa Russell
Satish K Pillai
David J Looney
Satya Dandekar
In vivo CD8+ T-cell suppression of siv viremia is not mediated by CTL clearance of productively infected cells.
PLoS Pathogens
title In vivo CD8+ T-cell suppression of siv viremia is not mediated by CTL clearance of productively infected cells.
title_full In vivo CD8+ T-cell suppression of siv viremia is not mediated by CTL clearance of productively infected cells.
title_fullStr In vivo CD8+ T-cell suppression of siv viremia is not mediated by CTL clearance of productively infected cells.
title_full_unstemmed In vivo CD8+ T-cell suppression of siv viremia is not mediated by CTL clearance of productively infected cells.
title_short In vivo CD8+ T-cell suppression of siv viremia is not mediated by CTL clearance of productively infected cells.
title_sort in vivo cd8 t cell suppression of siv viremia is not mediated by ctl clearance of productively infected cells
url http://europepmc.org/articles/PMC2813272?pdf=render
work_keys_str_mv AT josephkwong invivocd8tcellsuppressionofsivviremiaisnotmediatedbyctlclearanceofproductivelyinfectedcells
AT matthewcstrain invivocd8tcellsuppressionofsivviremiaisnotmediatedbyctlclearanceofproductivelyinfectedcells
AT rodinporrata invivocd8tcellsuppressionofsivviremiaisnotmediatedbyctlclearanceofproductivelyinfectedcells
AT elizabethreay invivocd8tcellsuppressionofsivviremiaisnotmediatedbyctlclearanceofproductivelyinfectedcells
AT sumathisankaranwalters invivocd8tcellsuppressionofsivviremiaisnotmediatedbyctlclearanceofproductivelyinfectedcells
AT carolinecignacio invivocd8tcellsuppressionofsivviremiaisnotmediatedbyctlclearanceofproductivelyinfectedcells
AT theresarussell invivocd8tcellsuppressionofsivviremiaisnotmediatedbyctlclearanceofproductivelyinfectedcells
AT satishkpillai invivocd8tcellsuppressionofsivviremiaisnotmediatedbyctlclearanceofproductivelyinfectedcells
AT davidjlooney invivocd8tcellsuppressionofsivviremiaisnotmediatedbyctlclearanceofproductivelyinfectedcells
AT satyadandekar invivocd8tcellsuppressionofsivviremiaisnotmediatedbyctlclearanceofproductivelyinfectedcells