CD73-mediated adenosine production by CD8 T cell-derived extracellular vesicles constitutes an intrinsic mechanism of immune suppression

• DOI: 10.1038/s41467-021-26134-w
• Publication Date: 2021-10-09T07:03:53Z
• Authors: Enja Schneider; Riekje Winzer; Anne Rissiek; Isabell Ricklefs; Catherine Meyer-S...; Franz L. Ricklefs; Andreas Bauche; Jochen Behrends; Rudolph Reimer; Santra Brenna; Hauke Wasielewski; Melchior Lauten; Björn Rissiek; Berta Puig; Filippo Cortesi; Tim Magnus; Ralf Fliegert; Christa E. Müller; Nicola Gagliani; Eva Tolosa
• Keywords: Extracellular vesicles

Abstract Immune cells at sites of inflammation are continuously activated by local antigens and cytokines, regulatory mechanisms must be enacted to control inflammation. The stepwise hydrolysis extracellular ATP ectonucleotidases CD39 CD73 generates adenosine, a potent immune suppressor. Here we report that human effector CD8 T contribute adenosine production releasing CD73-containing vesicles upon activation. These have AMPase activity, the resulting mediates suppression independently cells. In addition, show isolated from synovial fluid patients with juvenile idiopathic arthritis cell in CD73-dependent manner. Our results suggest generation activation is an intrinsic mechanism complements cell-mediated inflamed tissue. Finally, our data underscore role cell-derived responses.