Cutting edge: Hematopoietic-derived APCs select regulatory T cells in thymus.
Recognition of self-peptide-MHC complexes by high-affinity TCRs and CD28 signaling are critical for the development of forkhead-winged helix box transcription factor 3(+) regulatory T cells (Tregs) in thymus. However, the type of APCs that are responsible for selecting Tregs has remained unclear. To dissect the role of hematopoietic-derived APCs (HCs) and thymic epithelial cells (TECs) in Treg selection, we constructed bone marrow chimeras with disrupted CD28/B7 signaling in the HC or TEC compartment and analyzed the generation of Tregs in the thymus. We found that both HCs and TECs were independently able to fully reconstitute the Treg population in the thymus of bone marrow chimeras. In addition, Treg selection requires the TCR signal and CD28 costimulation presented in cis on the same APC type in vivo. This study demonstrates a new role, to our knowledge, for HCs in the development of Tregs in thymus.
Román
Eulogia
E
Department of Immunology, University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA. eulogia.roman@uth.tmc.edu
Shino
Hanabuchi
H
Qin
F Xiao-Feng
FX
Liu
Yong Jun
YJ
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology* / Q000378:metabolism; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D018106:CD28 Antigens; D011948:Receptors, Antigen, T-Cell
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