Protein Kinase C-ϑ Mediates Negative Feedback on Regulatory T Cell Function.

T cell receptor (TCR)-dependent regulatory T cell (Treg) activity controls effector T cell (Teff) function and is inhibited by the inflammatory cytokine tumor necrosis factor-α (TNF-α). Protein kinase C-ϑ (PKC-ϑ) recruitment to the immunological synapse is required for full Teff activation. In contrast, PKC-ϑ was sequestered away from the Treg immunological synapse. Furthermore, PKC-ϑ blockade enhanced Treg function, demonstrating PKC-ϑ inhibits Treg- -mediated suppression. Inhibition of PKC-ϑ protected Treg from inactivation by TNF-α, restored activity of defective Treg from rheumatoid arthritis patients, and enhanced protection of mice from inflammatory colitis. Treg freed of PKC-ϑ-mediated inhibition can function in the presence of inflammatory cytokines and thus have therapeutic potential in control of inflammatory diseases. [ABSTRACT FROM AUTHOR]