title: Human CD4+CD25+ regulatory T cells share equally complex and comparable repertoires with CD4+CD25- counterparts.
abstract: CD4(+)CD25(+) T cells are critical mediators of peripheral immune tolerance. However, many developmental and functional characteristics of these cells are unknown, and knowledge of human regulatory T cells is particularly limited. To better understand how human CD4(+)CD25(+) T cells develop and function, we examined the diversity of CD4(+)CD25(+) and CD4(+)CD25(-) T cell repertoires in both thymus and peripheral blood. Levels of T receptor excision circles (TREC) were comparable in purified CD4(+)CD25(+) and CD4(+)CD25(-) thymic populations, but were significantly higher than those in samples derived from peripheral blood, consistent with murine studies demonstrating thymic development of CD4(+)CD25(+) regulatory T cells. Surprisingly, CD4(+)CD25(-) T cells isolated from peripheral blood had greater TREC quantities than their CD4(+)CD25(+) counterparts, supporting the possibility of extrathymic expansion as well. CD4(+)CD25(+) and CD4(+)CD25(-) T cells from a given individual showed overlapping profiles with respect to diversity by Vbeta staining and spectratyping. Interestingly, CD4(+)CD25(+) T cells have lower quantities of CD3 than CD4(+)CD25(-) T cells. Collectively, these data suggest that human CD4(+)CD25(+) T cells recognize a similar array of Ags as CD4(+)CD25(-) T cells. However, reduced levels of TCR on regulatory T cells suggest different requirements for activation and may contribute to how the immune system regulates whether a particular response is suppressed or augmented.
authors.affiliation: Division of Stem Cell Transplantation, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Kasow
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Chen
authors.forename: James
authors.initials: J
authors.lastname: Knowles
authors.forename: David
authors.initials: D
authors.lastname: Wichlan
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
authors.forename: Janice M
authors.initials: JM
authors.lastname: Riberdy
mesh_terms: D017252:CD3 Complex / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002469:Cell Separation; D002648:Child; D005434:Flow Cytometry; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis* / Q000097:blood; D013194:Staining and Labeling; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D017252:CD3 Complex; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015375:Receptors, Interleukin-2