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Regulatory T Cells Inhibit Protein Kinase C Recruitment to the Immune Synapse of Naive T Cells with the Same Antigen Specificity¹

Adriana Sumoza-Toledo^*, Alfred D. Eaton and Adelaida Sarukhan^2,*

^* Department of Immunology, Institute of Biomedical Investigation, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico; and Institut National de la Santé et de la Recherche Médicale, Unité 591, Centre Hospitalier Universitaire Necker, Paris, France

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 (PKC) 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 PKC 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 PKC recruitment in the effector T cell may be a common regulatory pathway leading to the absence of NF-B activation and contributing to the block of IL-2 secretion characteristic of immune suppression.

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