title: CD4+ CD25+ regulatory T cells inhibit the maturation but not the initiation of an autoantibody response.
abstract: To investigate the mechanism by which T regulatory (Treg) cells may control the early onset of autoimmunity, we have used an adoptive transfer model to track Treg, Th, and anti-chromatin B cell interactions in vivo. We show that anti-chromatin B cells secrete Abs by day 8 in vivo upon provision of undeviated, Th1- or Th2-type CD4+ T cell help, but this secretion is blocked by the coinjection of CD4+ CD25+ Treg cells. Although Treg cells do not interfere with the initial follicular entry or activation of Th or B cells at day 3, ICOS levels on Th cells are decreased. Furthermore, Treg cells must be administered during the initial phases of the Ab response to exert full suppression of autoantibody production. These studies indicate that CD25+ Treg cells act to inhibit the maturation, rather than the initiation, of autoantibody responses.
authors.affiliation: The Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: Michele L
authors.initials: ML
authors.lastname: Fields
authors.forename: Brian D
authors.initials: BD
authors.lastname: Hondowicz
authors.forename: Michele H
authors.initials: MH
authors.lastname: Metzgar
authors.forename: Simone A
authors.initials: SA
authors.lastname: Nish
authors.forename: Gina N
authors.initials: GN
authors.lastname: Wharton
authors.forename: Cristina C
authors.initials: CC
authors.lastname: Picca
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Caton
authors.forename: Jan
authors.initials: J
authors.lastname: Erikson
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002843:Chromatin / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D006388:Hemagglutinins / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D002843:Chromatin; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D006388:Hemagglutinins; D015375:Receptors, Interleukin-2