title: Origin and T cell receptor diversity of Foxp3+CD4+CD25+ T cells.
abstract: Foxp3(+)CD4(+)CD25(+) regulatory T cells can differentiate from Foxp3(-)CD4(+) medullary thymocytes and Foxp3(-)CD4(+) naive T cells. However, the impact of these two processes on size and composition of the peripheral repertoire of regulatory T cells is unclear. Here we followed the fate of individual Foxp3(+)CD4(+)CD25(+) thymocytes and T cells in vivo in T cell receptor (TCR) transgenic mice that express a restricted but polyclonal repertoire of TCRs. By utilizing high-throughput single-cell analysis, we showed that Foxp3(+)CD4(+) peripheral T cells were derived from thymic precursors that expressed a different TCRs than Foxp3(-)CD4(+) medullary thymocytes and Foxp3(-)CD4(+) T cells. Furthermore, the diversity of TCRs on Foxp3(+)CD4(+) regulatory T cells exceeded the diversity of TCRs on Foxp3(-)CD4(+) naive T cells, even in mice that lack expression of tissue-specific antigens. Our results imply that higher TCR diversity on Foxp3(+) regulatory T cells helps these cells to match the specificities of autoreactive and naive T cells.
authors.affiliation: Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta, Georgia 30912, USA.
authors.forename: Rafal
authors.initials: R
authors.lastname: Pacholczyk
authors.forename: Hanna
authors.initials: H
authors.lastname: Ignatowicz
authors.forename: Piotr
authors.initials: P
authors.lastname: Kraj
authors.forename: Leszek
authors.initials: L
authors.lastname: Ignatowicz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000276:immunology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D001324:Autoantigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2