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Regulation of Regulatory T Cells: Role of Dendritic Cells and Toll-Like Receptors

Dieter Kabelitz, MD
Institute of Immunology, UK S-H Campus Kiel, Michaelisstr. 5, D-24105 Kiel, Germany

Hans-Heinrich Oberg
Institute of Immunology, University Hospital Schleswig-Holstein Campus Kiel, Kiel, Germany

Daniela Wesch
Institute of Immunology, University Hospital Schleswig-Holstein Campus Kiel, Kiel, Germany

ABSTRACT

Regulatory T cells (Treg) are characterized by high-level surface CD25 and intracellular FoxP3 expression. Treg are instrumental in the maintenance of peripheral immune tolerance and the control of adaptive immune responses. Naturally occuring Treg suppress T-cell responses by cell contact-dependent mechanisms, whereas induced regulatory cells, including Tr1 cells, secrete inhibitory cytokines such as transforming growth factor (TGF)-β and interleukin-10. The interplay between Treg and antigen-responsive T cells is modulated by dendritic cells (DC). Whereas immature myeloid precursors of DC suppress T-cell activation per se and immature DC support Treg development, mature DC can override Treg-mediated suppression in vitro and in vivo. Mature DC activated through Toll-like receptor (TLR) pattern recognition receptors produce proinflammatory cytokines, including interleukin-6, which render responder T cells refractory to the suppressive effect of Treg. In addition, Treg also express certain TLR, and the activation and/or suppressor function of Treg is modulated directly by the respective ligands. In this review, we discuss current models of how signals delivered through innate immune receptors in response to pathogen-associated molecular patterns affect adaptive immune responses via modulation of Treg function.