title: New insights into HIV-1 specific cytotoxic T-lymphocyte responses in exposed, persistently seronegative Kenyan sex workers.
abstract: A clearer understanding of HIV-1 specific immune responses in highly-exposed, persistently seronegative (HEPS) subjects is important in developing models of HIV-1 protective immunity. HIV-1 specific cytotoxic T-lymphocytes (CTL) have been described in a cohort of HEPS Kenyan sex workers, and recent work has further elucidated these responses. CTL specific for HIV-1 Env were found in the blood of over half the sex workers meeting criteria for HIV resistance, and in some women recognized unmapped epitopes. The proportion of women with Env-specific CTL increased with the duration of uninfected HIV exposure, suggesting that these responses were acquired over time. CD8+ lymphocyte responses directed against predefined HIV-1 CTL epitopes from various HIV-1 genes were found in the blood and genital tract of >50% resistant sex workers, at a ten-fold lower frequency than in infected subjects. The epitope specificity of CD8+ responses differs between HEPS and HIV infected women, and in HEPS the maintenance of responses appears to be dependent on persistent HIV exposure. Several HIV-1 'resistant' sex workers have become HIV infected over the past 6 years, possibly related to waning of pre-existing HIV-specific CTL, and infection has often been associated with a switch in the epitope specificity of CD8+ responses. These findings suggest that vaccine-induced protective HIV immunity is a realistic goal, but that vaccine strategies of boosting or persistent antigen may be necessary for long-lived protection.
authors.affiliation: Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya. rupertkaul@hotmail.com
authors.forename: R
authors.initials: R
authors.lastname: Kaul
authors.forename: S L
authors.initials: SL
authors.lastname: Rowland-Jones
authors.forename: J
authors.initials: J
authors.lastname: Kimani
authors.forename: K
authors.initials: K
authors.lastname: Fowke
authors.forename: T
authors.initials: T
authors.lastname: Dong
authors.forename: P
authors.initials: P
authors.lastname: Kiama
authors.forename: J
authors.initials: J
authors.lastname: Rutherford
authors.forename: E
authors.initials: E
authors.lastname: Njagi
authors.forename: F
authors.initials: F
authors.lastname: Mwangi
authors.forename: T
authors.initials: T
authors.lastname: Rostron
authors.forename: J
authors.initials: J
authors.lastname: Onyango
authors.forename: J
authors.initials: J
authors.lastname: Oyugi
authors.forename: K S
authors.initials: KS
authors.lastname: MacDonald
authors.forename: J J
authors.initials: JJ
authors.lastname: Bwayo
authors.forename: F A
authors.initials: FA
authors.lastname: Plummer
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D015331:Cohort Studies; D000939:Epitopes / Q000235:genetics; D005260:Female; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology; D015752:Genes, env; D018023:HIV Seronegativity / Q000276:immunology*; D006679:HIV Seropositivity / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007630:Kenya; D008969:Molecular Sequence Data; D011477:Sex Work; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013997:Time Factors
chemical_list: D000939:Epitopes; D015686:Gene Products, env