Skip to Main content Skip to Navigation
Journal articles

HIV Controllers Maintain a Population of Highly Efficient Th1 Effector Cells in Contrast to Patients Treated in the Long Term.

Abstract : HIV controllers are rare individuals who spontaneously control HIV replication in the absence of antiretroviral therapy. To identify parameters of the CD4 response that may contribute to viral control rather than merely reflect a persistently low viremia, we compared the T helper profiles in two groups of patients with more than 10 years of viral suppression: HIV controllers from the Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) CO18 cohort (n = 26) and efficiently treated patients (n = 16). Cells specific for immunodominant Gag and cytomegalovirus (CMV) peptides were evaluated for the production of 10 cytokines and cytotoxicity markers and were also directly quantified ex vivo by major histocompatibility complex (MHC) class II tetramer staining. HIV controller CD4(+) T cells were characterized by a higher frequency of gamma interferon (IFN-γ) production, perforin(+)/CD107a(+) expression, and polyfunctionality in response to Gag peptides. While interleukin 4 (IL-4), IL-17, and IL-21 production did not differ between groups, the cells of treated patients produced more IL-10 in response to Gag and CMV peptides, pointing to persistent negative immunoregulation after long-term antiretroviral therapy. Gag293 tetramer-positive cells were detected at a high frequency (0.12%) and correlated positively with IFN-γ-producing CD4(+) T cells in the controller group (R = 0.73; P = 0.003). Tetramer-positive cells were fewer in the highly active antiretroviral therapy (HAART) group (0.04%) and did not correlate with IFN-γ production, supporting the notion of a persistent immune dysfunction in HIV-specific CD4(+) T cells of treated patients. In conclusion, HIV controllers maintained a population of highly efficient Th1 effectors directed against Gag in spite of a persistently low antigenemia, while patients treated in the long term showed a loss of CD4 effector functions.
Document type :
Journal articles
Complete list of metadatas

https://hal-pasteur.archives-ouvertes.fr/pasteur-00733917
Contributor : Cécile Pham <>
Submitted on : Wednesday, March 20, 2013 - 7:00:07 AM
Last modification on : Wednesday, September 16, 2020 - 5:04:54 PM
Long-term archiving on: : Friday, March 31, 2017 - 1:25:39 PM

File

author-ms-figs-vingert-chakrab...
Files produced by the author(s)

Identifiers

Citation

Benoît Vingert, Daniela Benati, Olivier Lambotte, Pierre de Truchis, Laurence Slama, et al.. HIV Controllers Maintain a Population of Highly Efficient Th1 Effector Cells in Contrast to Patients Treated in the Long Term.. Journal of Virology, American Society for Microbiology, 2012, 86 (19), pp.10661-74. ⟨10.1128/JVI.00056-12⟩. ⟨pasteur-00733917⟩

Share

Metrics

Record views

593

Files downloads

756