title: Immune activation in the female genital tract during HIV infection predicts mucosal CD4 depletion and HIV shedding.
abstract: Plasma viral load predicts genital tract human immunodeficiency virus (HIV) shedding in HIV-infected women. We investigated whether local mucosal T-cell activation (HLA-DR, CD38, CCR5, and Ki67) contributed to HIV shedding in the genital tracts of HIV-infected women. We showed that cervical cytobrush-derived T cells expressed higher frequencies of T-cell activation markers (CD38+ and HLA-DR+) than blood-derived T cells. Expression was significantly higher in HIV-infected women than in uninfected women. We found that the frequency of activated proliferating cervical T cells (Ki67+; Ki67+CCR5+) broadly predicted HIV shedding in the genital tract in HIV-infected women, independently of plasma viral loads. Furthermore, activated cervical T cells (HLA-DR+CD38+ and HLA-DR+CCR5+) and local HIV shedding were independently associated with CD4 depletion in the genital tract. These data suggest that the presence of high frequencies of activated T cells in the female genital mucosa during HIV infection facilitates both local HIV shedding and CD4 T-cell depletion.
authors.affiliation: Institute of Infectious Disease and Molecular Medicine, Cape Town, South Africa.
authors.forename: Heather B
authors.initials: HB
authors.lastname: Jaspan
authors.forename: Lenine
authors.initials: L
authors.lastname: Liebenberg
authors.forename: Willem
authors.initials: W
authors.lastname: Hanekom
authors.forename: Wendy
authors.initials: W
authors.lastname: Burgers
authors.forename: David
authors.initials: D
authors.lastname: Coetzee
authors.forename: Anna-Lise
authors.initials: AL
authors.lastname: Williamson
authors.forename: Francesca
authors.initials: F
authors.lastname: Little
authors.forename: Landon
authors.initials: L
authors.lastname: Myer
authors.forename: Robert W
authors.initials: RW
authors.lastname: Coombs
authors.forename: Don
authors.initials: D
authors.lastname: Sodora
authors.forename: Jo-Ann
authors.initials: JA
authors.lastname: Passmore
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002584:Cervix Uteri / Q000166:cytology / Q000276:immunology / Q000821:virology*; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D008213:Lymphocyte Activation; D019562:Viral Load; D017201:Virus Shedding / Q000276:immunology*