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Persistent expansion and Th1-like skewing of HIV-specific circulating T follicular helper cells during antiretroviral therapy.

ABSTRACT: BACKGROUND:Untreated HIV infection leads to alterations in HIV-specific CD4+ T cells including increased expression of co-inhibitory receptors (IRs) and skewing toward a T follicular helper cell (Tfh) signature. However, which changes are maintained after suppression of viral replication with antiretroviral therapy (ART) is poorly known. METHODS:We analyzed blood CD4+ T cells specific to HIV and comparative viral antigens in ART-treated people using a cytokine-independent activation-induced marker assay alone or in combination with functional readouts. FINDINGS:In intra-individual comparisons, HIV-specific CD4+ T cells were characterized by a larger fraction of circulating Tfh (cTfh) cells than CMV- and HBV-specific cells and preferentially expressed multiple IRs and showed elevated production of the Tfh cytokines CXCL13 and IL-21. In addition, HIV-specific cTfh exhibited a predominant Th1-like phenotype and function when compared to cTfh of other specificities, contrasting with a reduction in Th1-functions in HIV-specific non-cTfh. Using longitudinal samples, we demonstrate that this distinct HIV-specific cTfh profile was induced during chronic untreated HIV infection, persisted on ART and correlated with the translation-competent HIV reservoir but not with the total HIV DNA reservoir. INTERPRETATION:Expansion and altered features of HIV-specific cTfh cells are maintained during ART and may be driven by persistent HIV antigen expression. FUNDING:This work was supported by the National Institutes of Health (NIH), the Canadian Institutes of Health Research (CIHR) and the FRQS AIDS and Infectious Diseases Network.

SUBMITTER: Niessl J

PROVIDER: S-EPMC7136607 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Persistent expansion and Th1-like skewing of HIV-specific circulating T follicular helper cells during antiretroviral therapy.

Niessl Julia J Baxter Amy E AE Morou Antigoni A Brunet-Ratnasingham Elsa E Sannier Gérémy G Gendron-Lepage Gabrielle G Richard Jonathan J Delgado Gloria-Gabrielle GG Brassard Nathalie N Turcotte Isabelle I Fromentin Rémi R Bernard Nicole F NF Chomont Nicolas N Routy Jean-Pierre JP Dubé Mathieu M Finzi Andrés A Kaufmann Daniel E DE

EBioMedicine 20200405

<h4>Background</h4>Untreated HIV infection leads to alterations in HIV-specific CD4<sup>+</sup> T cells including increased expression of co-inhibitory receptors (IRs) and skewing toward a T follicular helper cell (Tfh) signature. However, which changes are maintained after suppression of viral replication with antiretroviral therapy (ART) is poorly known.<h4>Methods</h4>We analyzed blood CD4<sup>+</sup> T cells specific to HIV and comparative viral antigens in ART-treated people using a cytokin ...[more]

PMID: 32268275

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Dataset Information

Persistent expansion and Th1-like skewing of HIV-specific circulating T follicular helper cells during antiretroviral therapy.

Publications

Persistent expansion and Th1-like skewing of HIV-specific circulating T follicular helper cells during antiretroviral therapy.

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