title: HIV Infection in Uncircumcised Men Is Associated With Altered CD8 T-cell Function But Normal CD4 T-cell Numbers in the Foreskin.
abstract: BACKGROUND
  Human immunodeficiency virus (HIV)-infected (HIV+) men are more susceptible to sexually transmitted infections, and may be superinfected by HIV. We hypothesized that HIV induces immune alterations in the foreskin that may impact the subsequent acquisition/clearance of genital coinfections.
  
  
  METHODS
  Foreskin tissue and blood were obtained from 70 HIV-uninfected and 20 HIV+ men undergoing circumcision. T cells were characterized by flow cytometry, immunohistochemistry, and polymerase chain reaction.
  
  
  RESULTS
  There was substantial influx of CD8 T-cells into the foreskins of HIV+ men (108.8 vs 23.1 cells/mm(2); P < .001); but foreskin CD4 T-cell density was unchanged (43.0 vs 33.7/mm(2); P = .67), despite substantial blood depletion (409.0 vs 877.8 cells/µL; P < .001). While frequencies of foreskin C-C chemokine receptor type 5(+) (CCR5(+)) T cells, T regulatory cells, and T-helper 17 cells were unaltered in HIV+ men, CD8 T-cell production of tumor necrosis factor α (TNFα) was decreased. HIV-specific CD8 T cells were present in the foreskins of HIV+ men, although their frequency and function was reduced compared to the blood.
  
  
  CONCLUSIONS
  Foreskin CD4 T-cell density and CCR5 expression were not reduced during HIV infection, perhaps explaining susceptibility to HIV superinfection. Foreskin CD8 T-cell density was increased, but decreased production of TNFα may enhance susceptibility to genital coinfections in HIV+ men.
authors.affiliation: Clinical Science Division, Department of Medicine, University of Toronto, Canada.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Prodger
authors.forename: Taha
authors.initials: T
authors.lastname: Hirbod
authors.forename: Ronald
authors.initials: R
authors.lastname: Gray
authors.forename: Godfrey
authors.initials: G
authors.lastname: Kigozi
authors.forename: Fred
authors.initials: F
authors.lastname: Nalugoda
authors.forename: Ronald
authors.initials: R
authors.lastname: Galiwango
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Reynolds
authors.forename: Sanja
authors.initials: S
authors.lastname: Huibner
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Wawer
authors.forename: David
authors.initials: D
authors.lastname: Serwadda
authors.forename: Rupert
authors.initials: R
authors.lastname: Kaul
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002944:Circumcision, Male; D016207:Cytokines / Q000378:metabolism*; D005434:Flow Cytometry; D052816:Foreskin / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D016207:Cytokines
keywords: HIV; T cells; circumcision; cytokines; sexually transmitted infections