Characterization of the immunological synapses formed by induced T regulatory cells (168.13)

Abstract

Abstract T regulatory cells (Tregs) play a vital role in the maintenance of self-tolerance and in the suppression of active immune responses. FoxP3+ Tregs arise naturally in the thymus, but can also be induced both in vivo and in vitro. The immunological synapses (IS) formed by induced Tregs (iTregs) have not been studied. We show that iTregs form either immunological kinapses or stable IS depending on the level of CD80 on the surface of APCs. As has been shown for natural Tregs, iTregs are capable of downmodulating the costimulatory ligand CD80 on the surface of dendritic cells (DCs) in an antigen-specific, CTLA-4-dependent manner. On the same timescale as CD80 downmodulation, iTregs transition from stable to motile contacts with DCs. Experiments utilizing supported planar bilayers containing pMHC, ICAM-1 and CD80 show that iTregs form motile immunological kinapses with a highly polarized cell shape in the presence of low levels of CD80. However, iTregs arrest and form stable IS when interacting with bilayers containing high levels of CD80. In experiments with blocking antibodies, we demonstrate that CD28-CD80, but not CTLA-4-CD80, interactions modulate iTreg motility. Thus, iTregs are capable of downmodulating costimulatory molecules on the surface of DCs, which in turn alters their motility.