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

Clin Exp Immunol. 2015 Jun;180(3):452-7. doi: 10.1111/cei.12603.


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.

Keywords: PD-1; fulminant type 1 diabetes; type 1A diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alleles
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism*
  • Case-Control Studies
  • 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
  • Gene Expression
  • Genotype
  • Humans
  • Japan
  • Leukocytes, Mononuclear
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Receptor / genetics
  • Programmed Cell Death 1 Receptor / metabolism*
  • RNA, Messenger / genetics
  • Young Adult


  • Programmed Cell Death 1 Receptor
  • RNA, Messenger