title: Viruses and cytotoxic T lymphocytes in type 1 diabetes.
abstract: Histopathological studies on pancreas tissues from individuals with recent-onset type 1 diabetes (T1D) consistently find that CD8 T cells substantially contribute to the formation of islet lesions. CD8 T cells reactive against islet-associated antigens can also be found in blood samples from T1D patients. Mechanistic studies on the pathogenic role of this T cell subset have mostly focused on two animal models, i.e., the non-obese diabetic mouse and the virally induced rat insulin promoter-lymphocytic choriomeningitis virus model. Data were obtained in support of a role for viral infection in expanding a population of diabetogenic cytotoxic T lymphocytes. In view of the theorized association of viral infection with initiation of islet autoimmunity and progression to clinically overt disease, CD8 T cells thus represent an attractive target for immunotherapy. We will review here arguments in favor of a pivotal role for CD8 T cells in driving T1D development and speculate on etiologic agents that may provoke their aberrant activation.
authors.affiliation: Type 1 Diabetes Center, The La Jolla Institute for Allergy and Immunology, CA, 92037, USA.
authors.forename: Ken T
authors.initials: KT
authors.lastname: Coppieters
authors.forename: Matthias G
authors.initials: MG
authors.lastname: von Herrath
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000276:immunology* / Q000628:therapy; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D006801:Humans; D007167:Immunotherapy; D007515:Islets of Langerhans / Q000276:immunology* / Q000821:virology; D008213:Lymphocyte Activation; D008216:Lymphocytic Choriomeningitis / Q000150:complications / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology* / Q000472:pathogenicity; D051379:Mice; D016688:Mice, Inbred NOD; D051381:Rats
chemical_list: D001324:Autoantigens