Adenosine deaminase regulates Treg expression in autologous T cell-dendritic cell cocultures from patients infected with HIV-1.

Regulatory T cells have an important role in immune suppression during HIV-1 infection. As regulatory T cells produce the immunomodulatory molecule adenosine, our aim here was to assess the potential of adenosine removal to revert the suppression of anti-HIV responses exerted by regulatory T cells. The experimental setup consisted of ex vivo cocultures of T and dendritic cells, to which adenosine deaminase, an enzyme that hydrolyzes adenosine, was added.

Adenosine deaminase enhances the immunogenicity of human dendritic cells from healthy and HIV-infected individuals.

ADA is an enzyme implicated in purine metabolism, and is critical to ensure normal immune function. Its congenital deficit leads to severe combined immunodeficiency (SCID). ADA binding to adenosine receptors on dendritic cell surface enables T-cell costimulation through CD26 crosslinking, which enhances T-cell activation and proliferation.

Adenosine deaminase potentiates the generation of effector, memory, and regulatory CD4+ T cells.

By interacting with CD26 on the CD4+ T cell surface and with the AdoR A(₂B) on the DC surface, ADA triggers a costimulatory signal for human T cells. The aim of this study was to know whether ADA-mediated costimulation plays a role in the differentiation of T cells. The results show that irrespective of its enzymatic activity and dependent on TNF-α, IFN-γ, and IL-6 action, ADA enhanced the differentiation of CD4+CD45RA+CD45RO⁻ naïve T cells toward CD4+CD25+CD45RO+ Teffs and CD4+CD45RA⁻CD45RO+ memory T cells.