title: Cutting edge: Hematopoietic-derived APCs select regulatory T cells in thymus.
abstract: 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.
authors.affiliation: Department of Immunology, University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA. eulogia.roman@uth.tmc.edu
authors.forename: Eulogia
authors.initials: E
authors.lastname: Román
authors.forename: Hanabuchi
authors.initials: H
authors.lastname: Shino
authors.forename: F Xiao-Feng
authors.initials: FX
authors.lastname: Qin
authors.forename: Yong Jun
authors.initials: YJ
authors.lastname: Liu
mesh_terms: 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
chemical_list: D018106:CD28 Antigens; D011948:Receptors, Antigen, T-Cell
references.citation: J Immunol. 2003 Oct 1;171(7):3348-52
references.pmid: 14500627
references.citation: J Exp Med. 2004 Oct 18;200(8):1039-49
references.pmid: 15492126
references.citation: Trends Immunol. 2003 Feb;24(2):77-81
references.pmid: 12547504
references.citation: J Immunol. 2008 Jun 15;180(12):7793-803
references.pmid: 18523243
references.citation: Immunol Rev. 2006 Aug;212:8-27
references.pmid: 16903903
references.citation: Nature. 2005 Aug 25;436(7054):1181-5
references.pmid: 16121185
references.citation: Nat Immunol. 2005 Feb;6(2):152-62
references.pmid: 15640801
references.citation: Nat Immunol. 2006 Apr;7(4):338-43
references.pmid: 16550196
references.citation: Immunity. 2000 Apr;12(4):431-40
references.pmid: 10795741
references.citation: Nat Immunol. 2007 Apr;8(4):351-8
references.pmid: 17322887
references.citation: Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11903-8
references.pmid: 18695219
references.citation: Proc Natl Acad Sci U S A. 2008 Dec 16;105(50):19869-74
references.pmid: 19073916
references.citation: Nat Immunol. 2001 Apr;2(4):301-6
references.pmid: 11276200
references.citation: J Exp Med. 1997 Feb 3;185(3):377-83
references.pmid: 9053438
references.citation: J Immunol. 1997 Mar 1;158(5):2150-5
references.pmid: 9036960