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

Abstract

Yin-Yang T Cell Signaling Immune responses are kept in check by CD4 + regulatory T cells (T reg ) that suppress other immune cells, including CD4 + effector T cells (T eff ). T reg and T eff cells have many signaling components in common, yet triggering through their T cell receptors (TCRs) leads to very different outcomes. Zanin-Zhorov et al. (p. 372 , published online 25 March) compared the recruitment of signaling molecules to the immunological synapse after TCR triggering in T reg and T eff cells. Although T reg cells do form synapses, signaling molecules that promote T eff activation, such as protein kinase C-θ (PKC-θ), were not recruited. Inhibition or depletion of PKC-θ in T reg cells led to suppressive activity against T eff cells, whereas costimulation enhanced PKC-θ recruitment and less suppression. Together, this suggests that PKC-θ is inflammatory in both T reg and T eff cells; however, by excluding it from the synapse, T reg cells are able to maintain suppression in the face of TCR signaling.