title: Quantitative impact of thymic selection on Foxp3+ and Foxp3- subsets of self-peptide/MHC class II-specific CD4+ T cells.
abstract: It is currently thought that T cells with specificity for self-peptide/MHC (pMHC) ligands are deleted during thymic development, thereby preventing autoimmunity. In the case of CD4(+) T cells, what is unclear is the extent to which self-peptide/MHC class II (pMHCII)-specific T cells are deleted or become Foxp3(+) regulatory T cells. We addressed this issue by characterizing a natural polyclonal pMHCII-specific CD4(+) T-cell population in mice that either lacked or expressed the relevant antigen in a ubiquitous pattern. Mice expressing the antigen contained one-third the number of pMHCII-specific T cells as mice lacking the antigen, and the remaining cells exhibited low TCR avidity. In mice lacking the antigen, the pMHCII-specific T-cell population was dominated by phenotypically naive Foxp3(-) cells, but also contained a subset of Foxp3(+) regulatory cells. Both Foxp3(-) and Foxp3(+) pMHCII-specific T-cell numbers were reduced in mice expressing the antigen, but the Foxp3(+) subset was more resistant to changes in number and TCR repertoire. Therefore, thymic selection of self-pMHCII-specific CD4(+) T cells results in incomplete deletion within the normal polyclonal repertoire, especially among regulatory T cells.
authors.affiliation: Department of Microbiology and Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. jjmoon@mgh.harvard.edu
authors.forename: James J
authors.initials: JJ
authors.lastname: Moon
authors.forename: Pradyot
authors.initials: P
authors.lastname: Dash
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Oguin
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: McClaren
authors.forename: H Hamlet
authors.initials: HH
authors.lastname: Chu
authors.forename: Paul G
authors.initials: PG
authors.lastname: Thomas
authors.forename: Marc K
authors.initials: MK
authors.lastname: Jenkins
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D017637:Clonal Deletion; D051858:Forkhead Transcription Factors / Q000032:analysis*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007108:Immune Tolerance; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology*
chemical_list: D001324:Autoantigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell