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

Nat Commun. 2019 Feb 18;10(1):823. doi: 10.1038/s41467-019-08801-1.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 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


  • IL2 protein, human
  • IL6 protein, human
  • Interleukin-2
  • Interleukin-6
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4
  • ADA protein, human
  • Adenosine Deaminase
  • Adenylyl Cyclases