title: T cell islet accumulation in type 1 diabetes is a tightly regulated, cell-autonomous event.
abstract: Type 1 diabetes is a T cell-mediated autoimmune disease, characterized by lymphocytic infiltration of the pancreatic islets. It is currently thought that islet antigen specificity is not a requirement for islet entry and that diabetogenic T cells can recruit a heterogeneous bystander T cell population. We tested this assumption directly by generating T cell receptor (TCR) retrogenic mice expressing two different T cell populations. By combining diabetogenic and nondiabetogenic or nonautoantigen-specific T cells, we demonstrate that bystander T cells cannot accumulate in the pancreatic islets. Autoantigen-specific T cells that accumulate in islets, but do not cause diabetes, were also unaffected by the presence of diabetogenic T cells. Additionally, 67% of TCRs cloned from nonobese diabetic (NOD) islet-infiltrating CD4(+) T cells were able to mediate cell-autonomous islet infiltration and/or diabetes when expressed in retrogenic mice. Therefore, islet entry and accumulation appears to be a cell-autonomous and tightly regulated event and is governed by islet antigen specificity.
authors.affiliation: Department of Immunology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Greig P
authors.initials: GP
authors.lastname: Lennon
authors.forename: Maria
authors.initials: M
authors.lastname: Bettini
authors.forename: Amanda R
authors.initials: AR
authors.lastname: Burton
authors.forename: Erica
authors.initials: E
authors.lastname: Vincent
authors.forename: Paula Y
authors.initials: PY
authors.lastname: Arnold
authors.forename: Pere
authors.initials: P
authors.lastname: Santamaria
authors.forename: Dario A A
authors.initials: DA
authors.lastname: Vignali
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism; D018014:Gene Transfer Techniques; D007515:Islets of Langerhans / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: D001324:Autoantigens