Most highly exposed seronegative men lack HIV-1-specific, IFN-gamma-secreting T cells.
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.
Hladik
Florian
F
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.
Desbien
Anthony
A
Lang
Jean
J
Wang
Lei
L
Ding
Yan
Y
Holte
Sarah
S
Wilson
Aaron
A
Xu
Younong
Y
Moerbe
Micky
M
Schmechel
Steve
S
McElrath
M Juliana
MJ
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
D018984:Epitopes, T-Lymphocyte; D007371:Interferon-gamma