title: An islet-homing NOD CD8+ cytotoxic T cell clone recognizes GAD65 and causes insulitis.
abstract: T cells play a central role in the development of diabetes both in man and in the non-obese diabetic (NOD) mouse. Both the CD4(+) and CD8(+) subsets of T cells are required for the normal development of IDDM in NOD mice. Islet reactive CD4(+) T cells play a clear pathogenic role as evidenced from the isolation of diabetogenic CD4(+) T cell clones. CD8(+) T cells seem to be involved in the initiation of diabetes as lack of these cells leads to protection from diabetes. We have isolated a GAD(65) reactive, cytotoxic CD8(+) T cell clone R1 that produces large quantities of IFNgamma and accelerates the onset of insulitis. This clone proliferates and produces IFNgamma in response to GAD(65) presenting APCs and kills GAD(65) presenting targets. Furthermore, it expresses TNFalpha, CD25, CD28, CD44, CD45 and LFA1, but not CD95L This is the first example of a GAD(65)specific CD8(+) T cell clone that accelerates the onset of the insulitis, although it does not appear to accelerate the onset of diabetes.
authors.affiliation: Hagedorn Research Institute, Niels Steensensvej 6, DK 2820, Gentofte, Denmark.
authors.forename: Nicoline
authors.initials: N
authors.lastname: Videbaek
authors.forename: Silvia
authors.initials: S
authors.lastname: Harach
authors.forename: Jenny
authors.initials: J
authors.lastname: Phillips
authors.forename: Patricia
authors.initials: P
authors.lastname: Hutchings
authors.forename: Patricia
authors.initials: P
authors.lastname: Ozegbe
authors.forename: Birgitte K
authors.initials: BK
authors.lastname: Michelsen
authors.forename: Anne
authors.initials: A
authors.lastname: Cooke
mesh_terms: D000818:Animals; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D007515:Islets of Langerhans / Q000276:immunology*; D007527:Isoenzymes / Q000276:immunology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D007371:Interferon-gamma; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2