title: CD25+ CD4+ T cells, expanded with dendritic cells presenting a single autoantigenic peptide, suppress autoimmune diabetes.
abstract: In the nonobese diabetic (NOD) mouse model of type 1 diabetes, the immune system recognizes many autoantigens expressed in pancreatic islet beta cells. To silence autoimmunity, we used dendritic cells (DCs) from NOD mice to expand CD25+ CD4+ suppressor T cells from BDC2.5 mice, which are specific for a single islet autoantigen. The expanded T cells were more suppressive in vitro than their freshly isolated counterparts, indicating that DCs from autoimmune mice can increase the number and function of antigen-specific, CD25+ CD4+ regulatory T cells. Importantly, only 5,000 expanded CD25+ CD4+ BDC2.5 T cells could block autoimmunity caused by diabetogenic T cells in NOD mice, whereas 10(5) polyclonal, CD25+ CD4+ T cells from NOD mice were inactive. When islets were examined in treated mice, insulitis development was blocked at early (3 wk) but not later (11 wk) time points. The expanded CD25+ CD4+ BDC2.5 T cells were effective even if administered 14 d after the diabetogenic T cells. Our data indicate that DCs can generate CD25+ CD4+ T cells that suppress autoimmune disease in vivo. This might be harnessed as a new avenue for immunotherapy, especially because CD25+ CD4+ regulatory cells responsive to a single autoantigen can inhibit diabetes mediated by reactivity to multiple antigens.
authors.affiliation: Laboratory of Cellular Physiology and Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
authors.forename: Kristin V
authors.initials: KV
authors.lastname: Tarbell
authors.forename: Sayuri
authors.initials: S
authors.lastname: Yamazaki
authors.forename: Kara
authors.initials: K
authors.lastname: Olson
authors.forename: Priscilla
authors.initials: P
authors.lastname: Toy
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Steinman
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D001324:Autoantigens / Q000276:immunology*; D015704:CD4 Antigens / Q000032:analysis*; D003713:Dendritic Cells / Q000502:physiology*; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control*; D005260:Female; D016130:Immunophenotyping; D007515:Islets of Langerhans / Q000473:pathology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D001324:Autoantigens; D015704:CD4 Antigens; D015375:Receptors, Interleukin-2