Low programmed cell death‐1 (PD‐1) expression in peripheral CD4+ T cells in Japanese patients with autoimmune type 1 diabetes. (15th May 2015)

• Record Type: Journal Article
• Authors: Fujisawa, R.; Haseda, F.; Tsutsumi, C.; Hiromine, Y.; Noso, S.; Kawabata, Y.; Mitsui, S.; Terasaki, J.; Ikegami, H.; Imagawa, A.; Hanafusa, T.
• Is Part Of: Clinical and experimental immunology. Volume 180:Number 3(2015:Jun.)
• Page Start: 452
• Page End: 457
• Publication Date: 2015-05-15
• Subjects: Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.12603
• Languages: English
• ISSNs: 0009-9104

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>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<sup>+</sup> T cells and the association between PD‐1 expression and the 7785C/T polymorphism of <italic>PDCD1, </italic> 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 <italic>PDCD1</italic> 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<sup>+</sup> T cells in patients with T1AD (mean: 4·2 <italic>vs.</italic> 6·0% in FT1D, <italic>P</italic> = 0·0450; <italic>vs.</italic> 5·8% in T2D, <italic>P =</italic> 0·0098; <italic>vs.</italic> 6·0% in HC, <italic>P</italic> = 0·0018). PD‐1 mRNA expression in CD4<sup>+</sup> 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 <italic>vs.</italic> 5·9%, <italic>P</italic> = 0·0016). Our results indicate that lower PD‐1 expression in CD4<sup>+</sup> T‐cells might contribute to the development of T1AD through T cell activation.</p> </abstract>