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. Marta Ruiz-Riol1,a, 
2. Anuska Llano1,a, 
3. Javier Ibarrondo9, 
4. Jennifer Zamarreño1,
5. Karina Yusim10, 
6. Vanessa Bach1, 
7. Beatriz Mothe1,2,8, 
8. Susana Perez-Alvarez4,
9. Marco A. Fernandez3, 
10. Gerard Requena3, 
11. Michael Meulbroek5, 
12. Ferran Pujol5, 
13. Agathe Leon6,
14. Patricia Cobarsi2, 
15. Bette T. Korber10, 
16. Bonaventura Clotet1,2,8, 
17. Carmela Ganoza11,
18. Jorge Sanchez11, 
19. Josep Coll1,2 and 
20. 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 Pujol, Badalona
4. ⁴Biokit Research and Development, Lliçà d'Amunt
5. ⁵BCN Checkpoint, Projecte dels NOMS–Hispanosida
6. ⁶HIVACAT, Hospital 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 Laboratory, New Mexico
11. ¹¹Asociacion Civil Impacta Salud y Educacion, Lima, 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

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

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

• © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail:journals.permissions@oup.com.