TY - JOUR
T1 - Alternative effector-function profiling identifies broad HIV-specific T-cell responses in highly HIV-exposed individuals who remain uninfected
AU - Ruiz-Riol, Marta
AU - Llano, Anuska
AU - Ibarrondo, Javier
AU - Zamarreño, Jennifer
AU - Yusim, Karina
AU - Bach, Vanessa
AU - Mothe, Beatriz
AU - Perez-Alvarez, Susana
AU - Fernandez, Marco A.
AU - Requena, Gerard
AU - Meulbroek, Michael
AU - Pujol, Ferran
AU - Leon, Agathe
AU - Cobarsi, Patricia
AU - Korber, Bette T.
AU - Clotet, Bonaventura
AU - Ganoza, Carmela
AU - Sanchez, Jorge
AU - Coll, Josep
AU - Brander, Christian
PY - 2015/1/1
Y1 - 2015/1/1
N2 - © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. 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.
AB - © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. 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.
KW - boosted flow cytometry
KW - highly exposed seronegative
KW - HIV infection
KW - T-cell responses
KW - Th1 cytokines
KW - Th17 cytokines
KW - Th2 cytokines
KW - toggled peptides
U2 - 10.1093/infdis/jiu534
DO - 10.1093/infdis/jiu534
M3 - Article
VL - 211
SP - 936
EP - 946
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 6
ER -