Circulating CXCR5+CXCR3+PD-1lo Tfh-like cells in HIV-1 controllers with neutralizing antibody breadth
Year: 2017
Type: article
Abstract: HIV-1–specific broadly neutralizing antibodies (bnAbs) typically develop in individuals with continuous high-level viral replication and increased immune activation, conditions that cannot be reproduced during prophylactic immunization. Understanding mechanisms supporting bnAb development in the absence of high-level viremia may be important for designing bnAb-inducing immunogens. Here, we show that the breadth of neutralizing antibody responses in HIV-1 controllers was associated with a relative enrichment of circulating CXCR5 + CXCR3 + PD-1 lo CD4 + T cells. These CXCR3 + PD-1 lo Tfh-like cells were preferentially induced in vitro by functionally superior dendritic cells from controller neutralizers, and able to secrete IL-21 and support B cells. In addition, these CXCR3 + PD-1 lo Tfh-like cells contained higher proportions of stem cell–like memory T cells, and upon antigenic stimulation differentiated into PD-1 hi Tfh-like cells in a Notch-dependent manner. Together, these data suggest that CXCR5 + CXCR3 + PD-1 lo cells represent a dendritic cell–primed precursor cell population for PD-1 hi Tfh-like cells that may contribute to the generation of bnAbs in the absence of high-level viremia.
Source: JCI Insight
Institutions: Ragon Institute of MGH, MIT and Harvard, Massachusetts Institute of Technology, Duke University, Vaccine & Gene Therapy Institute of Florida, Drexel University, Howard Hughes Medical Institute, Centre Hospitalier de l’Université de Montréal, Université de Montréal, Brigham and Women's Hospital, Massachusetts General Hospital
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,100
Awards: A systems biology approach to fingerprint HIV immune defense in Elite Controllers, A systems biology approach to fingerprint HIV immune defense in Elite Controllers, T memory stem cell aging in HIV-1 infection, G4405334196, The General Hospital Corporation d/b/a Massachusetts General Hospital - to support a project designed to define the baseline status of the immune system immediately before, and during the earliest events in HIV infectio..., Boosting anti-HIV immunity through manipulation of Tfh function., Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, Molecular basis of myelomonocytic receptor function in HIV-1 infection, "Bottom - Up" Profiling of Interacting Cellular Systems, A Microengraving Technology for the Study of Latently HIV-infected Primary Cells, Immunoregulatory Function of Myelomonocytic Receptors in HIV-1 Infection, An integrated multiplexed genomic assay for low input clinical samples1, Inhibitors of host kinases as molecular targets for immune defense against HIV-1, G9000208279, G9000235933
OpenAlex ID: W2580686727