Differentiation of type 1 T regulatory cells (Tr1) by tolerogenic DC-10 requires the IL-10–dependent ILT4/HLA-G pathway

Blood - Tập 116 - Trang 935-944 - 2010
Silvia Gregori1, Daniela Tomasoni1, Valentina Pacciani1,2, Miriam Scirpoli3, Manuela Battaglia1,3, Chiara Francesca Magnani1, Ehud Hauben1, Maria-Grazia Roncarolo1,4
1Department of Regenerative Medicine, Stem Cells, and Gene Therapy, San Raffaele Telethon Institute for Gene Therapy, Milan, Italy;
2University Department of Pediatrics (DPUO), Bambino Gesù Children's Hospital, Rome, Italy;
3Department of Immunology, Transplantation, and Infectious Diseases, Diabetes Research Institute, Milan, Italy; and
4Università Vita-Salute San Raffaele, Milan, Italy

Tóm tắt

Abstract

Type 1 T regulatory (Tr1) cells suppress immune responses in vivo and in vitro and play a key role in maintaining tolerance to self- and non–self-antigens. Interleukin-10 (IL-10) is the crucial driving factor for Tr1 cell differentiation, but the molecular mechanisms underlying this induction remain unknown. We identified and characterized a subset of IL-10–producing human dendritic cells (DCs), termed DC-10, which are present in vivo and can be induced in vitro in the presence of IL-10. DC-10 are CD14+, CD16+, CD11c+, CD11b+, HLA-DR+, CD83+, CD1a−, CD1c−, express the Ig-like transcripts (ILTs) ILT2, ILT3, ILT4, and HLA-G antigen, display high levels of CD40 and CD86, and up-regulate CD80 after differentiation in vitro. DC-10 isolated from peripheral blood or generated in vitro are potent inducers of antigen-specific IL-10–producing Tr1 cells. Induction of Tr1 cells by DC-10 is IL-10–dependent and requires the ILT4/HLA-G signaling pathway. Our data indicate that DC-10 represents a novel subset of tolerogenic DCs, which secrete high levels of IL-10, express ILT4 and HLA-G, and have the specific function to induce Tr1 cells.


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