Human Circulating PD-1+CXCR3−CXCR5+ Memory Tfh Cells Are Highly Functional and Correlate with Broadly Neutralizing HIV Antibody Responses

By M. Locci, C. Havenar-Daughton, E. Landais, Jennifer E. Wu, M. Kroenke, C. L. Arlehamn, L. Su, R. Cubas, Mark M. Davis, Alessandro Sette and 3 more. Immunity, 2013

843 citations recorded by the source corpus.

SUMMARY The vast majority of currently licensed human vaccines work on the basis of long-term protective antibody responses. It is now conceivable that an antibody-dependent HIV vaccine might be possible, given the discovery of HIV broadly neutralizing antibodies (bnAbs) in some HIV-infected individuals. However, these antibodies are difficult to develop and have characteristics indicative of a high degree of affinity maturation in germinal centers (GCs). CD4+ T follicular helper (Tfh) cells are specialized for B cell help and necessary for GCs. Therefore, the development of HIV bnAbs might depend on Tfh cells. Here, we identified in normal individuals a subpopulation of circulating memory PD-1+CXCR5+ CD4+ T cells that are resting memory cells most related to bona fide GC Tfh cells by gene expression profile, cytokine profile, and functional properties. Importantly, the frequency of these cells correlated with the development of bnAbs against HIV in a large cohort of HIV+ individuals.

Subfields: Immunology, Virology

View Paper: https://www.semanticscholar.org/paper/75041529e734c86d5aadaa878b923a0205586d9a

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In Immunology

1. Shane Crotty
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Citations in the corpus

• T follicular helper cell biology: A decade of discovery and diseases (2019, background): “The large majority of flu-specific activated cTfh cells are CXCR3+ and CXCR3+ cTfh cells correlate with acute anti-influenza IgG (Bentebibel et al., 2013); however, CXCR3+ memory cTfh cells are particularly poor providers of B cell help in vitro (Locci et al., 2013; Morita et al., 2011).”
• T follicular helper cell differentiation, function, and roles in disease (2014, background): “Tfh cell frequencies are associated with the amount and quality of antibody responses against SIV (simian immunodeficiency virus, a close relative to HIV) in SIV-infected macaques (Petrovas et al., 2012).”
• Follicular Helper T Cells. (2016, background): “The frequency of circulating CXCR5+ PD-1+ Tfh cells, with a transcription profile similar to GC Tfh cells, was associated with the production of high-affinity bNAbs in HIV-infected individuals (61).”
• Mapping the Diversity of Follicular Helper T Cells in Human Blood and Tonsils Using High-Dimensional Mass Cytometry Analysis. (2015, background): “Future studies should also address the functional relevance of the numerous subtypes of TFH cells, as well as determine their association with clinical parameters such as age or response to vaccination similar to previous studies (Bentebibel et al., 2013; He et al., 2013; Locci et al., 2013).”