title: Most highly exposed seronegative men lack HIV-1-specific, IFN-gamma-secreting T cells.
abstract: Naturally acquired cellular immunity in individuals who have been exposed to HIV-1 but have remained uninfected may hold clues for the design of an effective HIV vaccine. To determine the presence and nature of such an HIV-1-specific immune response, we evaluated the quantity and fine specificity of HIV-1-reactive IFN-gamma-secreting T cells in a group of highly exposed seronegative men having sex with men. All 46 ES reported frequent unprotected anal sex with known HIV-1-infected partners at enrollment, and high risk activities continued in at least one-half of the volunteers for up to >6 years of observation. Despite the high frequency of unprotected anal intercourse and potential HIV-1 exposure, the vast majority of individuals demonstrated no or very low numbers of HIV-1-specific, IFN-gamma-secreting T cells. Even when HIV-1 epitopes were presented by peptide-pulsed autologous dendritic cells in 15 of the highest risk volunteers, HIV-1-specific T cells remained infrequent, and the proportion of responders was not significantly different from that in a lower risk seronegative control cohort. Only PBMC from two individuals who have remained uninfected to date exhibited distinctly positive responses. However, these responses rarely persisted over time, single epitope specificities were identified in only one volunteer, and HIV-1-specific memory T cell clones did not expand in vitro. HIV-1-specific, IFN-gamma-secreting T cells are thus unlikely to substantially contribute to resistance against infection in most exposed seronegative men having sex with men.
authors.affiliation: Program in Infectious Diseases, Clinical Research Division, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, D3-100, Seattle, WA 98109, USA.
authors.forename: Florian
authors.initials: F
authors.lastname: Hladik
authors.forename: Anthony
authors.initials: A
authors.lastname: Desbien
authors.forename: Jean
authors.initials: J
authors.lastname: Lang
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Ding
authors.forename: Sarah
authors.initials: S
authors.lastname: Holte
authors.forename: Aaron
authors.initials: A
authors.lastname: Wilson
authors.forename: Younong
authors.initials: Y
authors.lastname: Xu
authors.forename: Micky
authors.initials: M
authors.lastname: Moerbe
authors.forename: Steve
authors.initials: S
authors.lastname: Schmechel
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D017951:Antigen Presentation; D002999:Clone Cells; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods / Q000592:standards; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000032:analysis / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism; D018023:HIV Seronegativity / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012309:Risk-Taking; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000821:virology
chemical_list: D018984:Epitopes, T-Lymphocyte; D007371:Interferon-gamma