Low programmed cell death‐1 (PD‐1) expression in peripheral CD4+ T cells in Japanese patients with autoimmune type 1 diabetes

• Published in: Clinical and experimental immunology Vol. 180; no. 3; pp. 452 - 457
• Main Authors: Fujisawa, R., Haseda, F., Tsutsumi, C., Hiromine, Y., Noso, S., Kawabata, Y., Mitsui, S., Terasaki, J., Ikegami, H., Imagawa, A., Hanafusa, T.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.06.2015; BlackWell Publishing Ltd
• Subjects: Adolescent; Adult; Aged; Alleles; Case-Control Studies; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 2 - immunology; Diabetes Mellitus, Type 2 - metabolism; Female; fulminant type 1 diabetes; Gene Expression; Genotype; Humans; Japan; Leukocytes, Mononuclear; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Male; Middle Aged; PD‐1; Programmed Cell Death 1 Receptor - genetics; Programmed Cell Death 1 Receptor - metabolism; RNA, Messenger - genetics; Translation; type 1A diabetes; Young Adult; Japan; fulminant type 1 diabetes; type 1A diabetes; PD-1
• ISSN: 0009-9104; 1365-2249; 1365-2249
• DOI: 10.1111/cei.12603

Summary 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.