Inhibiting the inhibitor of the inhibitor: blocking PKC-theta to enhance regulatory T cell function

Protein kinase C (PKC-theta), one of many PKC isoforms expressed in T cells, is important for the activation of mature effector T cells. During T cell activation, PKC-theta is recruited to the interface between the T cell and the activating cellular interaction partner, the antigen-presenting cell or a synthetic substitute thereof. New evidence establishes that PKC-theta function differs in regulatory T cells, a T cell subset that suppresses the function of effector T cells. In regulatory T cells, PKC-theta inhibits their function and, intriguingly, is sequestered from the activating cellular interface. This finding raises several questions of general interest. Does PKC-theta function overlap with that of other PKC family members? What are the functionally critical distinctions in the similar signaling systems of effector and regulatory T cells? Does the divergent localization of PKC-theta in regulatory T cells drive function?