Regulatory T Cell Suppression Is Potentiated by Target T Cells in a Cell Contact, IL-35-and IL-10-Dependent Manner

Regulatory T cells (T-reg) are believed to suppress conventional T cell (T-conv) proliferation in vitro in a contact-dependent, cytokine-independent manner, based in part on experiments in which T-reg and T-conv are separated by a permeable membrane. We show that the production of IL-35, a novel inhibitory cytokine expressed by natural T-reg, increases substantially following contact with T-conv, Surprisingly, T-reg were able to mediate potent suppression of T-conv across a permeable membrane when placed in direct contact with T-conv in the upper chamber of a Transwell plate. Suppression was IL-35 and IL-10 dependent, and T-conv activation was required for maximal potentiation of T-reg suppression. These data suggest that it is the induction of suppression, rather than the function of T-reg that is obligatorily contact dependent. The Journal of Immunology, 2009, 182: 6121-6128.