title: Low CTLA-4 expression in CD4+ helper T-cells in patients with fulminant type 1 diabetes.
abstract: Fulminant type 1 diabetes is a novel subtype of type 1 diabetes characterized by a remarkably abrupt onset of insulin-deficient hyperglycemia. An accelerated immune reaction has been suggested as the cause of markedly rapid beta cell loss in this disease, but the precise mechanism has not been clarified. We analyzed the expression of cytotoxic T lymphocyte antigen 4 (CTLA-4) in CD4(+) helper T-cells in 16 patients with fulminant type 1 diabetes, 14 patients with type 1A diabetes, 10 patients with type 2 diabetes and 20 normal control subjects. There was a significant reduction in CTLA-4 expression in CD4(+) helper T-cells from patients with fulminant type 1 diabetes (P<0.05) compared with the other three groups. Low CTLA-4 expression was also observed in both CD4(+)CD25(high) T-cells and CD4(+)CD25(-) T-cells. There was a significant negative correlation between the proliferation of CD4(+)CD25(-) T-cells and the levels of CTLA-4. Intracellular expression of CTLA-4 in CD4(+) helper T-cells was not correlated with two CTLA-4 polymorphisms. In conclusion, the expression of CTLA-4 in CD4(+) helper T-cells was low in patients with fulminant type 1 diabetes.
authors.affiliation: Department of Internal Medicine (I), Osaka Medical College, Japan.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Haseda
authors.forename: Akihisa
authors.initials: A
authors.lastname: Imagawa
authors.forename: Yuko
authors.initials: Y
authors.lastname: Murase-Mishiba
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sano
authors.forename: Suzue
authors.initials: S
authors.lastname: Hirano-Kuwata
authors.forename: Hironori
authors.initials: H
authors.lastname: Ueda
authors.forename: Jungo
authors.initials: J
authors.lastname: Terasaki
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hanafusa
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D060908:CTLA-4 Antigen; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger