Journal article
Circulating CXCR5+CXCR3+PD-1lo Tfh-like cells in HIV-1 controllers with neutralizing antibody breadth
JCI insight, v 2(2), pp e89574-e89574
26 Jan 2017
PMID: 28138558
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
The development of neutralizing breadth under controlled viremia is associated with a population of circulating CXCR3+CXCR5+PD-1Lo TFH-like cells.
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Details
- Title
- Circulating CXCR5+CXCR3+PD-1lo Tfh-like cells in HIV-1 controllers with neutralizing antibody breadth
- Creators
- Enrique Martin-Gayo - Ragon Institute of MGH, MIT and HarvardJacqueline Cronin - Ragon Institute of MGH, MIT and HarvardTaylor Hickman - Ragon Institute of MGH, MIT and HarvardZhengyu Ouyang - Ragon Institute of MGH, MIT and HarvardMadelene Lindqvist - Ragon Institute of MGH, MIT and HarvardKellie E. Kolb - Massachusetts Institute of TechnologyJulian Schulze zur Wiesch - Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), Duke University, Durham, North Carolina, USA. MIT Institute for Medical Engineering & Science (IMES) and Chemistry, Cambridge, Massachusetts, USA. University Medical Center Hamburg, Hamburg, Germany. Vaccine & Gene Therapy Institute of Florida, Port St. Lucie, Florida, USA. Drexel University, Division of Infectious Diseases and HIV Medicine, Philadelphia, Pennsylvania, USA. Howard Hughes Medical Institute, Chevy Chase, Maryland, USA. Centre hospitalier de l’Université de Montréal (CHUM) Research Center, University of Montreal, Montreal, Quebec, Canada. Infectious Disease Divisions, Brigham and Women’s Hospital and Massachusetts General Hospital, Boston, Massachusetts, USARafael Cubas - Vaccine & Gene Therapy Institute of FloridaFilippos Porichis - Ragon Institute of MGH, MIT and HarvardAlex K. Shalek - Massachusetts Institute of TechnologyJan van Lunzen - University Medical Center Hamburg, Hamburg, Germany.Elias K. Haddad - Drexel UniversityBruce D. Walker - Howard Hughes Medical InstituteDaniel E. Kaufmann - Centre Hospitalier de l’Université de MontréalMathias Lichterfeld - Brigham and Women's HospitalXu G. Yu - Ragon Institute of MGH, MIT and Harvard
- Publication Details
- JCI insight, v 2(2), pp e89574-e89574
- Publisher
- American Society for Clinical Investigation
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Infectious Diseases (and HIV Medicine); Drexel University
- Web of Science ID
- WOS:000393592200008
- Other Identifier
- 991020099780204721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Medicine, Research & Experimental