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Persistent expansion and Th1-like skewing of HIV-specific circulating T follicular helper cells during antiretroviral therapy
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 ant...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136607/ https://www.ncbi.nlm.nih.gov/pubmed/32268275 http://dx.doi.org/10.1016/j.ebiom.2020.102727 |
Sumario: | 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. |
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