title: TGF-beta 1 plays an important role in the mechanism of CD4+CD25+ regulatory T cell activity in both humans and mice.
abstract: In previous studies, we have shown that murine CD4+CD25+ regulatory T cells produce high levels of TGF-beta1 in a cell surface and/or secreted form, and blockade of such TGF-beta1 by anti-TGF-beta curtails the ability of these cells to suppress CD25- T cell proliferation and B cell Ig production in in vitro suppressor assays. In further support for the role of TGF-beta1 in suppression by CD4+CD25+ T cells, we show in this study that another TGF-beta1-blocking molecule, recombinant latency-associated peptide of TGF-beta1 (rLAP), also reverses suppression by mouse CD4+CD25+ T cells as well as their human counterparts, CD4+CD25(high) T cells. In addition, we show that CD25- T cells exposed to CD4+CD25+ T cells in vitro manifest activation of Smad-2 and induction of CD103, the latter a TGF-beta-inducible surface integrin. In further studies, we show that while CD4+CD25+ T cells from TGF-beta1-deficient mice can suppress CD25- T cell proliferation in vitro, these cells do not protect recipient mice from colitis in the SCID transfer model in vivo, and, in addition, CD4+LAP+, but not CD4+LAP- T cells from normal mice protect recipient mice from colitis in this model. Together, these studies demonstrate that TGF-beta1 produced by CD4+CD25+ T cells is involved in the suppressor activity of these cells, particularly in their ability to regulate intestinal inflammation.
authors.affiliation: Mucosal Immunity Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11N238, 10 Center Drive, Bethesda, MD 20892, USA.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakamura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kitani
authors.forename: Ivan
authors.initials: I
authors.lastname: Fuss
authors.forename: Aasta
authors.initials: A
authors.lastname: Pedersen
authors.forename: Naohiko
authors.initials: N
authors.lastname: Harada
authors.forename: Hajime
authors.initials: H
authors.lastname: Nawata
authors.forename: Warren
authors.initials: W
authors.lastname: Strober
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003092:Colitis / Q000235:genetics / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D010446:Peptide Fragments / Q000096:biosynthesis / Q000494:pharmacology; D011485:Protein Binding / Q000276:immunology; D011498:Protein Precursors / Q000096:biosynthesis / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D018125:Receptors, Transforming Growth Factor beta / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D053773:Transforming Growth Factor beta1
chemical_list: D018836:Inflammation Mediators; D010446:Peptide Fragments; D011498:Protein Precursors; D015375:Receptors, Interleukin-2; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1