title: Immune tolerance. Regulatory T cells generated early in life play a distinct role in maintaining self-tolerance.
abstract: Aire is an important regulator of immunological tolerance, operating in a minute subset of thymic stromal cells to induce transcripts encoding peptides that guide T cell selection. Expression of Aire during a perinatal age window is necessary and sufficient to prevent the multiorgan autoimmunity characteristic of Aire-deficient mice. We report that Aire promotes the perinatal generation of a distinct compartment of Foxp3(+)CD4(+) regulatory T (Treg) cells, which stably persists in adult mice. This population has a role in maintaining self-tolerance, a transcriptome and an activation profile distinguishable from those of Tregs produced in adults. Underlying the distinct Treg populations are age-dependent, Aire-independent differences in the processing and presentation of thymic stromal-cell peptides, resulting in different T cell receptor repertoires. Our findings expand the notion of a developmentally layered immune system.
authors: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. Aging Intervention Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, 305-806, South Korea.
authors: Siyoung
authors: S
authors: Yang
authors: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors: Noriyuki
authors: N
authors: Fujikado
authors: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors: Dmitriy
authors: D
authors: Kolodin
authors: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston MA 02115, USA. cbdm@hms.harvard.edu.
authors: Christophe
authors: C
authors: Benoist
authors: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston MA 02115, USA. cbdm@hms.harvard.edu.
authors: Diane
authors: D
authors: Mathis
mesh_terms: D000818:Animals; D015551:Autoimmunity; D015704:CD4 Antigens / Q000032:analysis; D051858:Forkhead Transcription Factors / Q000032:analysis; D051379:Mice; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D017634:Self Tolerance / Q000235:genetics*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D059467:Transcriptome; D000096927:AIRE Protein
chemical_list: D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors; D000096927:AIRE Protein; C498833:Foxp3 protein, mouse