title: Both retention and recirculation contribute to long-lived regulatory T-cell accumulation in the thymus.
abstract: Natural Treg cells acquire their lineage-determining transcription factor Foxp3 during development in the thymus and are important in maintaining immunologic tolerance. Here, we analyzed the composition of the thymic Treg-cell pool using RAG2-GFP/FoxP3-RFP dual reporter mice and found that a population of long-lived GFP(-) Treg cells exists in the thymus. These long-lived Treg cells substantially increased with age, to a point where they represent >90% of the total thymic Treg-cell pool at 6 months of age. In contrast, long-lived conventional T cells remained at ∼ 15% of the total thymic pool at 6 months of age. Consistent with these studies, we noticed that host-derived Treg cells represented a large fraction (∼ 10%) of the total thymic Treg-cell pool in bone marrow chimeras, suggesting that long-lived Treg cells also reside in the thymus of these mice. The pool of long-lived Treg cells in the thymus was sustained by retention of Treg cells in the thymus and by recirculation of peripheral Treg cells back into the thymus. These long-lived thymic Treg cells suppressed T-cell proliferation to an equivalent extent to splenic Treg cells. Together, these data demonstrate that long-lived Treg cells accumulate in the thymus by both retention and recirculation.
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: EnJun
authors.initials: E
authors.lastname: Yang
authors.forename: Tao
authors.initials: T
authors.lastname: Zou
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Leichner
authors.forename: Shirley L
authors.initials: SL
authors.lastname: Zhang
authors.forename: Taku
authors.initials: T
authors.lastname: Kambayashi
mesh_terms: D000375:Aging / Q000276:immunology; D000818:Animals; D049109:Cell Proliferation; D051379:Mice; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland; D013997:Time Factors
keywords: Cellular immunology; Regulatory T cells; Thymic recirculation; Thymic retention; Thymopoiesis