title: Development of CD25(+) T cells secreting transforming growth factor-beta1 by altered peptide ligands expressed as self-antigens.
abstract: This study demonstrates that CD4(+) T cells specific for an altered self-antigen differentiate to T cells secreting transforming growth factor (TGF)-beta1. In this study, we utilized mice expressing an altered peptide ligand containing a single amino acid substitution of moth cytochrome c 88-103 peptide. In these mice, antigen-specific T cells escaping thymic negative selection differentiated into T cells with an effector/memory phenotype, CD44(high), CD45RB(low), CD62L(-) and CD25(intermediate). The expression of CD25 and high levels of CD44 was initiated in the thymus during the development from CD4(+)CD8(+) to CD4(+); a large proportion of maturing CD4(+) thymocytes expressed both CD25 and high levels of CD44. Upon antigen stimulation, CD4(+) T cells derived from these mice did not proliferate or secrete IL-2, but secreted TGF-beta1. Neutralizing antibodies to TGF-beta1 reversed the impaired proliferative responses to the antigen, suggesting that TGF-beta1 secreted from these T cells negatively regulates T cell responses.
authors.affiliation: Research Institute for Biological Sciences, Science University of Tokyo, 2669 Yamazaki, Noda City, Chiba 278-0022, Japan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Yamashiro
authors.forename: Nobumichi
authors.initials: N
authors.lastname: Hozumi
authors.forename: Naoko
authors.initials: N
authors.lastname: Nakano
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D017635:Clonal Anergy; D003574:Cytochrome c Group / Q000235:genetics / Q000276:immunology; D018960:Hyaluronan Receptors / Q000378:metabolism; D007156:Immunologic Memory; D066298:In Vitro Techniques; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009036:Moths; D010455:Peptides / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D053773:Transforming Growth Factor beta1
chemical_list: D001324:Autoantigens; D003574:Cytochrome c Group; D018960:Hyaluronan Receptors; D008024:Ligands; D010455:Peptides; D015375:Receptors, Interleukin-2; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1