title: Low programmed cell death-1 (PD-1) expression in peripheral CD4(+) T cells in Japanese patients with autoimmune type 1 diabetes.
abstract: Programmed cell death-1 (PD-1) is a co-stimulatory molecule that inhibits T cell proliferation. We aimed to clarify PD-1 expression in CD4(+) T cells and the association between PD-1 expression and the 7785C/T polymorphism of PDCD1, with a focus on the two subtypes of type 1 diabetes, type 1A diabetes (T1AD) and fulminant type 1 diabetes (FT1D), in the Japanese population. We examined 22 patients with T1AD, 15 with FT1D, 19 with type 2 diabetes (T2D) and 29 healthy control (HC) subjects. Fluorescence-activated cell sorting (FACS) and real-time PCR were utilized to analyse PD-1 expression quantitatively. Genotyping of 7785C/T in PDCD1 was performed using the TaqMan method in a total of 63 subjects (21 with T1AD, 15 with FT1D and 27 HC). FACS revealed a significant reduction in PD-1 expression in CD4(+) T cells in patients with T1AD (mean: 4.2 vs. 6.0% in FT1D, P=0.0450; vs. 5.8% in T2D, P=0.0098; vs. 6.0% in HC, P=0.0018). PD-1 mRNA expression in CD4(+) T cells was also significantly lower in patients with T1AD than in the HC subjects. Of the 63 subjects, PD-1 expression was significantly lower in individuals with the 7785C/C genotype than in those with the C/T and T/T genotypes (mean: 4.1 vs. 5.9%, P=0.0016). Our results indicate that lower PD-1 expression in CD4(+) T-cells might contribute to the development of T1AD through T cell activation.
authors: Department of Internal Medicine (I), Osaka Medical College, Takatsuki, Japan.
authors: R
authors: R
authors: Fujisawa
authors: Department of Internal Medicine (I), Osaka Medical College, Takatsuki, Japan.
authors: F
authors: F
authors: Haseda
authors: Department of Internal Medicine (I), Osaka Medical College, Takatsuki, Japan.
authors: C
authors: C
authors: Tsutsumi
authors: Department of Endocrinology, Metabolism and Diabetes, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
authors: Y
authors: Y
authors: Hiromine
authors: Department of Endocrinology, Metabolism and Diabetes, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
authors: S
authors: S
authors: Noso
authors: Department of Endocrinology, Metabolism and Diabetes, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
authors: Y
authors: Y
authors: Kawabata
authors: Department of Internal Medicine (I), Osaka Medical College, Takatsuki, Japan.
authors: S
authors: S
authors: Mitsui
authors: Department of Internal Medicine (I), Osaka Medical College, Takatsuki, Japan.
authors: J
authors: J
authors: Terasaki
authors: Department of Endocrinology, Metabolism and Diabetes, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
authors: H
authors: H
authors: Ikegami
authors: Department of Internal Medicine (I), Osaka Medical College, Takatsuki, Japan.|Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Japan.
authors: A
authors: A
authors: Imagawa
authors: Department of Internal Medicine (I), Osaka Medical College, Takatsuki, Japan.
authors: T
authors: T
authors: Hanafusa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D007564:Japan; D007963:Leukocytes, Mononuclear; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D055815:Young Adult
chemical_list: D061026:Programmed Cell Death 1 Receptor; D012333:RNA, Messenger
keywords: PD-1; fulminant type 1 diabetes; type 1A diabetes