REGULATORY T CELL SUPPRESSION IS POTENTIATED BY TARGET T CELLS IN A CELL CONTACT IL-35- AND IL-10-DEPENDENT MANNER

摘要

Regulatory T cells (Treg) are believed to suppress conventional T cell (Tconv) proliferation in vitro in a contact-dependent, cytokine-independent manner, based in part on experiments in which Treg and Tconv are separated by a permeable membrane. We show that the production of interleukin-35 (IL-35), a novel inhibitory cytokine expressed by natural Treg, increases substantially following contact with Tconv. Surprisingly, Treg were able to mediate potent suppression of Tconv across a permeable membrane when placed in direct contact with Tconv in the upper chamber of a Transwell™ plate. Suppression was IL-35- and IL-10-dependent, and Tconv activation was required for maximal potentiation of Treg suppression. These data suggest that it is the ‘induction’ of suppression, rather than the ‘function’ of Treg that is obligatorily contact-dependent.