title: Vaccination with live attenuated simian immunodeficiency virus causes dynamic changes in intestinal CD4+CCR5+ T cells.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  In naive controls, modest frequencies of intestinal CD4+CCR5+ T cells were predominantly found within the LPL TTrM-1 and IEL TTrM-2 subsets. At day 3, LPL and IEL CD4+CCR5+ TEM 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+ TEM to less differentiated TTrM-2 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 TN cells were detected concurrent with greatly increased CD4+CCR5+ LPL TTrM-2 and IEL TEM cells at day 125, yet SIV RNA plasma loads remained low.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Biotherapeutics Group, National Institute of Biological Standards and Control/Health Protection Agency, Potters Bar, Hertfordshire, UK. richard.stebbings@nibsc.hpa.org.uk.
authors.forename: Bo
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authors.lastname: Li
authors.forename: Neil
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authors.lastname: Berry
authors.forename: Claire
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authors.lastname: Ferguson
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authors.lastname: Smith
authors.forename: Joanna
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authors.lastname: Hall
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authors.lastname: Page
authors.forename: Ruby
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authors.lastname: Elsley
authors.forename: Mark
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authors.lastname: Robinson
authors.forename: Neil
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authors.lastname: Almond
authors.forename: Richard
authors.initials: R
authors.lastname: Stebbings