martes, 14 de octubre de 2014

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

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



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

  1. Christian Brander1,7,8
+Author Affiliations
  1. 1HIVACAT, Irsicaixa AIDS Research Institute, Autonomous University of Barcelona
  2. 2Fundació Lluita Contra La Sida, Hospital Universitari Germans Trias i Pujol
  3. 3Flow Cytometry Facility, Health Sciences Research Institute Germans Trias i PujolBadalona
  4. 4Biokit Research and Development, Lliçà d'Amunt
  5. 5BCN Checkpoint, Projecte dels NOMS–Hispanosida
  6. 6HIVACATHospital Clinic–Fundació Clinic
  7. 7Institució Catalana de Recerca i Estudis Avancats (ICREA)Barcelona
  8. 8University of Vic, Spain
  9. 9Center for HIV Prevention Research, University of California–Los Angeles
  10. 10Los Alamos National LaboratoryNew Mexico
  11. 11Asociacion Civil Impacta Salud y EducacionLima, Peru
  1. Correspondence: Christian Brander, PhD, Laboratori de Retrovirologia, Fundació IrsiCaixa, Hospital Universitari Germans Trias i Pujol, Ctra del Canyet s/n, 08916 Badalona, Barcelona, Catalonia, Spain (cbrander@irsicaixa.es).
  1. Presented in part: HIV Vaccines (X5), Keystone Symposia on Molecular and Cellular Biology, Keystone, Colorado, 21–26 March 2012.
  2. a M. R.-R. and A. L. contributed equally to this report.

Abstract

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.

Key words

  • Received May 15, 2014.
  • Accepted September 9, 2014.

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