Vaccination with live attenuated simian immunodeficiency virus causes dynamic changes in intestinal CD4+CCR5+ T cells

<p>Abstract</p> <p>Background</p> <p>Vaccination with live attenuated SIV can protect against detectable infection with wild-type virus. We have investigated whether target cell depletion contributes to the protection observed. Following vaccination with live attenuated...

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Main Authors: Elsley William, Quartey-Papafio Ruby, Page Mark, Hall Joanna, Smith Deborah, Ferguson Deborah, Ham Claire, Berry Neil, Li Bo, Robinson Mark, Almond Neil, Stebbings Richard
Format: Article
Language:English
Published: BMC 2011-02-01
Series:Retrovirology
Online Access:http://www.retrovirology.com/content/8/1/8
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author Elsley William
Quartey-Papafio Ruby
Page Mark
Hall Joanna
Smith Deborah
Ferguson Deborah
Ham Claire
Berry Neil
Li Bo
Robinson Mark
Almond Neil
Stebbings Richard
author_facet Elsley William
Quartey-Papafio Ruby
Page Mark
Hall Joanna
Smith Deborah
Ferguson Deborah
Ham Claire
Berry Neil
Li Bo
Robinson Mark
Almond Neil
Stebbings Richard
author_sort Elsley William
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Vaccination with live attenuated SIV can protect against detectable infection with wild-type virus. We have investigated whether target cell depletion contributes to the protection observed. Following vaccination with live attenuated SIV the frequency of intestinal CD4+CCR5+ T cells, an early target of wild-type SIV infection and destruction, was determined at days 3, 7, 10, 21 and 125 post inoculation.</p> <p>Results</p> <p>In naive controls, modest frequencies of intestinal CD4+CCR5+ T cells were predominantly found within the LPL T<sub>TrM-1 </sub>and IEL T<sub>TrM-2 </sub>subsets. At day 3, LPL and IEL CD4+CCR5+ T<sub>EM </sub>cells were dramatically increased whilst less differentiated subsets were greatly reduced, consistent with activation-induced maturation. CCR5 expression remained high at day 7, although there was a shift in subset balance from CD4+CCR5+ T<sub>EM </sub>to less differentiated T<sub>TrM-2 </sub>cells. This increase in intestinal CD4+CCR5+ T cells preceded the peak of SIV RNA plasma loads measured at day 10. Greater than 65.9% depletion of intestinal CD4+CCR5+ T cells followed at day 10, but overall CD4+ T cell homeostasis was maintained by increased CD4+CCR5- T cells. At days 21 and 125, high numbers of intestinal CD4+CCR5- naive T<sub>N </sub>cells were detected concurrent with greatly increased CD4+CCR5+ LPL T<sub>TrM-2 </sub>and IEL T<sub>EM </sub>cells at day 125, yet SIV RNA plasma loads remained low.</p> <p>Conclusions</p> <p>This increase in intestinal CD4+CCR5+ T cells, following vaccination with live attenuated SIV, does not correlate with target cell depletion as a mechanism of protection. Instead, increased intestinal CD4+CCR5+ T cells may correlate with or contribute to the protection conferred by vaccination with live attenuated SIV.</p>
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spelling doaj.art-feed2c17b99f4e6884ac48ee5d2f72382022-12-22T00:10:39ZengBMCRetrovirology1742-46902011-02-0181810.1186/1742-4690-8-8Vaccination with live attenuated simian immunodeficiency virus causes dynamic changes in intestinal CD4+CCR5+ T cellsElsley WilliamQuartey-Papafio RubyPage MarkHall JoannaSmith DeborahFerguson DeborahHam ClaireBerry NeilLi BoRobinson MarkAlmond NeilStebbings Richard<p>Abstract</p> <p>Background</p> <p>Vaccination with live attenuated SIV can protect against detectable infection with wild-type virus. We have investigated whether target cell depletion contributes to the protection observed. Following vaccination with live attenuated SIV the frequency of intestinal CD4+CCR5+ T cells, an early target of wild-type SIV infection and destruction, was determined at days 3, 7, 10, 21 and 125 post inoculation.</p> <p>Results</p> <p>In naive controls, modest frequencies of intestinal CD4+CCR5+ T cells were predominantly found within the LPL T<sub>TrM-1 </sub>and IEL T<sub>TrM-2 </sub>subsets. At day 3, LPL and IEL CD4+CCR5+ T<sub>EM </sub>cells were dramatically increased whilst less differentiated subsets were greatly reduced, consistent with activation-induced maturation. CCR5 expression remained high at day 7, although there was a shift in subset balance from CD4+CCR5+ T<sub>EM </sub>to less differentiated T<sub>TrM-2 </sub>cells. This increase in intestinal CD4+CCR5+ T cells preceded the peak of SIV RNA plasma loads measured at day 10. Greater than 65.9% depletion of intestinal CD4+CCR5+ T cells followed at day 10, but overall CD4+ T cell homeostasis was maintained by increased CD4+CCR5- T cells. At days 21 and 125, high numbers of intestinal CD4+CCR5- naive T<sub>N </sub>cells were detected concurrent with greatly increased CD4+CCR5+ LPL T<sub>TrM-2 </sub>and IEL T<sub>EM </sub>cells at day 125, yet SIV RNA plasma loads remained low.</p> <p>Conclusions</p> <p>This increase in intestinal CD4+CCR5+ T cells, following vaccination with live attenuated SIV, does not correlate with target cell depletion as a mechanism of protection. Instead, increased intestinal CD4+CCR5+ T cells may correlate with or contribute to the protection conferred by vaccination with live attenuated SIV.</p>http://www.retrovirology.com/content/8/1/8
spellingShingle Elsley William
Quartey-Papafio Ruby
Page Mark
Hall Joanna
Smith Deborah
Ferguson Deborah
Ham Claire
Berry Neil
Li Bo
Robinson Mark
Almond Neil
Stebbings Richard
Vaccination with live attenuated simian immunodeficiency virus causes dynamic changes in intestinal CD4+CCR5+ T cells
Retrovirology
title Vaccination with live attenuated simian immunodeficiency virus causes dynamic changes in intestinal CD4+CCR5+ T cells
title_full Vaccination with live attenuated simian immunodeficiency virus causes dynamic changes in intestinal CD4+CCR5+ T cells
title_fullStr Vaccination with live attenuated simian immunodeficiency virus causes dynamic changes in intestinal CD4+CCR5+ T cells
title_full_unstemmed Vaccination with live attenuated simian immunodeficiency virus causes dynamic changes in intestinal CD4+CCR5+ T cells
title_short Vaccination with live attenuated simian immunodeficiency virus causes dynamic changes in intestinal CD4+CCR5+ T cells
title_sort vaccination with live attenuated simian immunodeficiency virus causes dynamic changes in intestinal cd4 ccr5 t cells
url http://www.retrovirology.com/content/8/1/8
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