title: Induction of allopeptide-specific human CD4+CD25+ regulatory T cells ex vivo.
abstract: Although CD4+CD25+ regulatory T cells are pivotal in the prevention of autoimmunity and appear to mediate transplantation tolerance, little is known concerning their antigen specificity. Here we describe the induction of a human CD4+CD25+ regulatory T-cell line specific for a defined peptide alloantigen (human leukocyte antigen A2 [HLA-A2] 138-170) by priming purified CD4+CD25+ cells ex vivo. The regulatory cells were anergic and retained their ability to suppress antigen-driven responses of CD4+CD25- cells. They inhibited not only interleukin 2 (IL-2) secretion by CD4+CD25- T cells specific for the same peptide but also direct alloresponse of naive CD4+CD25- T cells stimulated by semiallogeneic dendritic cells (DCs) in the presence of the peptide ("linked suppression"). They also suppressed the response of CD4+ T cells specific for viral and bacterial antigens. The suppressive T-cell line showed sustained high CD25 expression. These findings suggest that peripheral CD4+CD25+ regulatory cells are a precommitted cell lineage from which cells with specificity for non-self-peptides can be selected. This may pave the way for inducing and expanding peptide antigen-specific regulatory T cells ex vivo for cell therapy in transplantation, allergy, and autoimmune disease.
authors.affiliation: Department of Immunology, Faculty of Medicine, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom.
authors.forename: Shuiping
authors.initials: S
authors.lastname: Jiang
authors.forename: Niels
authors.initials: N
authors.lastname: Camara
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lombardi
authors.forename: Robert I
authors.initials: RI
authors.lastname: Lechler
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000166:cytology* / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000276:immunology; D000939:Epitopes; D015789:HLA-A2 Antigen / Q000032:analysis / Q000276:immunology; D006389:Hemagglutinins, Viral / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013745:Tetanus Toxoid / Q000276:immunology
chemical_list: D015704:CD4 Antigens; D016207:Cytokines; D000939:Epitopes; D015789:HLA-A2 Antigen; D006389:Hemagglutinins, Viral; D015375:Receptors, Interleukin-2; D013745:Tetanus Toxoid