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 ()
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Virginie Tardif: Drexel University
Roshell Muir: Drexel University
Rafael Cubas: Genentech
Marita Chakhtoura: Drexel University
Peter Wilkinson: Case Western Reserve University
Talibah Metcalf: Drexel University
Rana Herro: La Jolla Institute for Allergy and Immunology
Elias K. Haddad: Drexel University

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-08801-1

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