Persistent expansion and Th1-like skewing of HIV-specific circulating T follicular helper cells during antiretroviral therapy
Julia Niessl, Amy E. Baxter, Antigoni Morou, Elsa Brunet‐Ratnasingham, Gérémy Sannier, Gabrielle Gendron‐Lepage, Jonathan Richard, Gloria-Gabrielle Delgado, Nathalie Brassard, Isabelle Turcotte, Rémi Fromentin, Nicole F. Bernard, Nicolas Chomont, Jean‐Pierre Routy, Mathieu Dubé, Andrés Finzi, Daniel E. Kaufmann
Abstract
BACKGROUND: 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: 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: 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.