Adenosine DeAminase-1 (ADA-1) improves Follicular helper T cell function and vaccine response [2]

Follicular helper T cells (Tfh) is indispensable for T-cell dependent antibody responses. Understanding the underlying mechanisms of their differentiation and function is critical for vaccine development. Using unique gene array analysis, we identified adenosine deaminase-1 (ADA-1), as a novel key molecule that drives Tfh helper program in proliferating germinal centers Tfh and circulatory Tfh cells following their interactions with B cells. ADA-1 expression and enzymatic activity is significantly higher in Tfh cells when compared to non-Tfh cells. Exogenous ADA-1 enhances the ability of less efficient cTfh and pro-follicular Tfh cells to provide B cell help, while pharmacological inhibition of ADA-1 activity impeded Tfh function and blunted antibody response. Importantly, in vivo use of recombinant ADA-1 as an adjuvant in a DNA-based HIV vaccine enhanced Tfh differentiation and improved the quantity and the quality of HIV-specific antibody response. Thus, ADA-1 represents a good target for the design of new vaccine strategy. There are 22 samples across 5 donor Tfh samples, and 4 pooled donor non-Tfh samples.