title: beta-cell antigen-specific CD56(+) NKT cells from type 1 diabetic patients: autoaggressive effector T cells damage human CD56(+) beta cells by HLA-restricted and non-HLA-restricted pathways.
abstract: Studies of type 1 diabetes indicate that autoaggressive T cells specific to beta-cell antigens, reaching certain threshold levels, may play critical roles in the development of the disease. Flow cytometric analyses found that autoreactive T-cell lines from patients induced by beta-cell antigens consisted of four major subsets (CD4(+)CD56(-), CD4(+)CD56(+), CD8(+)CD56(-), and CD8(+)CD56(+)) and that CD56(+) NKT cells might be derived from CD56(-) T cells. Moreover, the proportion of CD56(+) NKT cells in the T-cell lines was influenced by time course of repeated antigen stimulation. beta-cell antigen-specific CD56(+) NKT (CD4(+) or CD8(+)) cells were more aggressive (HLA-restricted and -unrestricted) effector cells lysing target cells such as K562, Jurkat, P815 plus anti-CD3 antibody, and autologous B cells sensitized by beta-cell peptides, when compared with their CD56(-) counterparts. beta-cell antigen- specific CD4(+)CD56(+) NKT cells showed non-HLA-restricted cytotoxicity to human beta cells, insulinoma cell line CM, and to islet cell lines TRM-6 and HP62 expressing CD56 but not to four CD56(-) pancreatic cell lines of non- islet origin. The CD4(+)CD56(+) NKT cells showed stronger cytotoxicity to CM, TRM-6 and HP62 cells than did CD4(+)CD56(-) T cells. Moreover, isotope-unlabelled CD56(+) cells and anti-CD56 antibodies were able to inhibit cytotoxicity of CD4(+)CD56(+) NKT to CD56(+) target cells. These results suggest that CD56(+) NKT cells are aggressive cytotoxic cells to beta cells and that CD56 expression might be associated with the aggressiveness of effector T cells and the susceptibility of target cells.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, B.C., Canada. daweiou@interchange.ubc.ca
authors.forename: Dawei
authors.initials: D
authors.lastname: Ou
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Metzger
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Wang
authors.forename: Paolo
authors.initials: P
authors.lastname: Pozzilli
authors.forename: Aubrey J
authors.initials: AJ
authors.lastname: Tingle
mesh_terms: D000293:Adolescent; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019002:CD56 Antigen / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D002648:Child; D003602:Cytotoxicity, Immunologic; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology*; D007527:Isoenzymes / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D015415:Biomarkers; D019002:CD56 Antigen; D006680:HLA Antigens; D000949:Histocompatibility Antigens Class II; D007527:Isoenzymes; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2