title: Induction of systemic HIV-1-specific cellular immune responses by oral exposure in the uninfected partner of discordant couples.
abstract: OBJECTIVE
  Previous studies have identified HIV-specific T-cell responses in HIV-exposed uninfected individuals (EUI). However, so far no study has investigated exposure through oral sex. Our aim was to investigate whether oral exposure is enough to induce a systemic HIV-specific T-cell response.
  
  
  METHODS
  Peripheral blood mononuclear cells were collected from 25 EUI living with a HIV-positive partner. Sexual behavior was described by the EUI in self-reported questionnaires. All clinical data of the infected partners were well documented.
  
  
  METHODS
  Peripheral blood mononuclear cells were stimulated with five different HIV peptide pools and HIV-specific T-cell responses were detected using the interferon-[gamma] enzyme-linked immunospot assay. Multiple cytokine production was studied longitudinally using flow cytometry intracellular cytokine assay.
  
  
  RESULTS
  The majority of the discordant couples reported having protected anal intercourse but unprotected oral sex. Three of the 23 tested EUI with evaluable results had HIV-Gag or Nef-specific T-cell responses. Two of the responders reported unprotected oral sex as the only route of exposure. The HIV-specific CD4+ and CD8+ T cells in the Gag-responder showed production of multiple cytokines. The magnitude of the responses decreased over time when the level of exposure, determined by the viral load in the partner, declined.
  
  
  CONCLUSIONS
  HIV exposure through oral sex is sufficient to induce systemic HIV-specific CD4+ and CD8+ T-cell immune responses in some uninfected individuals. Further investigation is needed to determine whether these responses have any protective role against HIV infection, or are merely evidence of exposure.
authors.affiliation: Department of Virology, Swedish Institute for Infectious Disease Control, and Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Sweden.
authors.forename: Carina L
authors.initials: CL
authors.lastname: Pérez
authors.forename: Klara
authors.initials: K
authors.lastname: Hasselrot
authors.forename: Göran
authors.initials: G
authors.lastname: Bratt
authors.forename: Kristina
authors.initials: K
authors.lastname: Broliden
authors.forename: Annika C
authors.initials: AC
authors.lastname: Karlsson
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D018023:HIV Seronegativity / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D009061:Mouth Mucosa / Q000276:immunology* / Q000821:virology; D012725:Sexual Behavior; D012747:Sexual Partners; D019562:Viral Load