Regulatory T cells inhibit protein kinase Cθ recruitment to the immune synapse of naive T cells with the same antigen specificity

The precise mechanisms by which regulatory T cells operate, particularly their effect on signaling pathways leading to T cell activation, are poorly understood. In this study we have used regulatory T (Treg) cells of known Ag specificity, generated in vivo, to address their effects on early activation events occurring in naive T cells of the same Ag specificity. We found that the Treg cells need to be present at the moment of priming to suppress activation and proliferation of the naive T cell. Furthermore, the Treg cells significantly inhibit the recruitment of protein kinase C theta (PKC theta) to the immune synapse of the naive T cell as long as both T cells are of the same Ag specificity and are contacting the same APC. Finally, naturally occurring CD4(+)25(+)T cells seem to have the same effect on PKCO recruitment in CD25(-) T cells of the same Ag specificity. These results suggest that although additional mechanisms of regulation are likely to exist, inhibition of PKCO recruitment in the effector T cell may be a common regulatory pathway leading to the absence of NF-kappa B activation and contributing to the block of IL-2 secretion characteristic of immune suppression.