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

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.

SUBMITTER: Tardif V

PROVIDER: S-EPMC6379489 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Adenosine DeAminase-1 (ADA-1) improves Follicular helper T cell function and vaccine response

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Adenosine DeAminase-1 (ADA-1) improves Follicular helper T cell function and vaccine response

Project description:Adenosine DeAminase-1 (ADA-1) improves Follicular helper T cell function and vaccine response

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