Alternative Effector-Function Profiling Identifies Broad HIV-Specific T-Cell Responses in Highly HIV-Exposed Individuals Who Remain Uninfected

作者：Ruiz Riol Marta; Llano Anuska; Ibarrondo Javier; Zamarreno Jennifer; Yusim Karina; Bach Vanessa; Mothe Beatriz; Perez Alvarez Susana; Fernandez Marco A; Requena Gerard; Meulbroek Michael; Pujol Ferran; Leon Agathe; Cobarsi Patricia; Korber Bette T; Clotet Bonaventura; Ganoza Carmela; Sanchez Jorge; Coll Josep; Brander Christian^*

来源：Journal of Infectious Diseases, 2015, 211(6): 936-946.

DOI：10.1093/infdis/jiu534

• boosted flow cytometry
• highly exposed seronegative
• HIV infection
• toggled peptides
• T-cell responses
• Th1 cytokines
• Th2 cytokines
• Th17 cytokines

The characterization of host immune responses to human immunodeficiency virus (HIV) in HIV controllers and individuals with high exposure but seronegativity to HIV (HESN) is needed to guide the development of effective preventive and therapeutic vaccine candidates. However, several technical hurdles severely limit the definition of an effective virus-specific T-cell response. By using a toggle-peptide approach, which takes HIV sequence diversity into account, and a novel, boosted cytokine staining/flow cytometry strategy, we here describe new patterns of T-cell responses to HIV that would be missed by standard assays. Importantly, this approach also allows detection of broad and strong virus-specific T-cell responses in HESN individuals that are characterized by a T-helper type 1 cytokine-like effector profile and produce cytokines that have been associated with potential control of HIV infection, including interleukin 10, interleukin 13, and interleukin 22. These results establish a novel approach to improve the current understanding of HIV-specific T-cell immunity and identify cellular immune responses and individual cytokines as potential markers of relative HIV resistance. As such, the findings also help develop similar strategies for more-comprehensive assessments of host immune responses to other human infections and immune-mediated disorders.

• 出版日期2015-3-15
• 单位Los Alamos