Logo image
Back
Adenosine deaminase-1 delineates human follicular helper T cell function and is altered with HIV
Journal article   Open access   Peer reviewed

Adenosine deaminase-1 delineates human follicular helper T cell function and is altered with HIV

Virginie Tardif, Roshell Muir, Rafael Cubas, Marita Chakhtoura, Peter Wilkinson, Talibah Metcalf, Rana Herro and Elias K Haddad
Nature communications, v 10(1), pp 823-823
18 Feb 2019
DOI: https://doi.org/10.1038/s41467-019-08801-1
PMID: 30778076
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1038/s41467-019-08801-1View
Published, Version of Record (VoR)CC BY V4.0,  Open

Abstract

Adenosine Deaminase - genetics Adenosine Deaminase - metabolism Adenylyl Cyclases - metabolism B-Lymphocytes - cytology Coculture Techniques Dipeptidyl Peptidase 4 - metabolism Germinal Center - metabolism HIV Infections - metabolism HIV Infections - pathology Humans Interleukin-2 - metabolism Interleukin-6 - metabolism T-Lymphocytes, Helper-Inducer - physiology T-Lymphocytes, Helper-Inducer - virology
Follicular helper T cells (Tfh) play critical roles instructing, and initiating T-cell dependent antibody responses. The underlying mechanisms that enhance their function is therefore critical for vaccine development. Here we apply gene array analysis identifying adenosine deaminase (ADA) as a key molecule that delineates a human Tfh helper program in proliferating circulating Tfh (cTfh) cells and Germinal Centers Tfh (GC-Tfh). ADA-1 expression and enzymatic activity are increased in efficient cTfh2-17/GC-Tfh cells. Exogenous ADA-1 enhances less efficient cTfh1 and pro-follicular Tfh PD-1+ CXCR5+ cells to provide B cell help, while pharmacological inhibition of ADA-1 activity impedes cTfh2-17/GC-Tfh function and diminished antibody response. Mechanistically, ADA-1 controls the Tfh program by influencing IL6/IL-2 production, controlling CD26 extracellular expression and could balance signals through adenosine receptors. Interestingly, dysfunctional Tfh from HIV infected-individual fail to regulate the ADA pathway. Thus, ADA-1 regulates human Tfh and represents a potential target for development of vaccine strategy.

Metrics

9 Record Views
26 citations in Web of Science
24 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Collaboration types
Industry collaboration
Domestic collaboration
Web of Science research areas
Immunology
Logo image