Abstract
Intrathymic negative selection and differentiation of regulatory T (Treg) cells are a cardinal event in central tolerance system. Thymic dendritic cells (DCs) are presumed to be capable of inducing the apoptosis of autoreactive T progenitor cells and of alternatively differentiating them into Treg cells. In spite of the presence of heterogenous DC subsets in thymus, similarly observed on other lymphoid organs such as lymph nodes and spleen, the role of each intrathymic DC subset in the central tolerance is still unclear. Recently, we demonstrated that mice deficient in a CC chemokine receptor, CCR2, exhibited a selective diminution in CD11c+CD11b+CD8-Sirpα+ conventional DC (cDC) subset in the thymus with an accumulation of T cells with reactivity against serum self-antigen in the periphery. Here, we further revealed that Sirpα+ cDCs in the thymus can selectively capture blood-borne antigens due to their unique intrathymic localization nearby small vessels and inside perivascular regions, and then induce the antigen-specific Treg cells and subsequent clonal deletion to an intravenously injected antigen, depending on the intensity of antigen presentation. Finally, we established a novel way to in vivo expand antigen-specific Treg cells via intrathymic antigen presentation by thymic Sirpα+ cDCs, which can dampen aberrant immune reaction in an antigen-specific manner.
