CD4+CD45RA−FoxP3high activated regulatory T cells are functionally impaired and related to residual insulin‐secreting capacity in patients with type 1 diabetes. (4th July 2013)

• Record Type: Journal Article
• Authors: Haseda, F.; Imagawa, A.; Murase‐Mishiba, Y.; Terasaki, J.; Hanafusa, T.
• Is Part Of: Clinical and experimental immunology. Volume 173:Number 2(2013:Aug.)
• Page Start: 207
• Page End: 216
• Publication Date: 2013-07-04
• Subjects: Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.12116
• Languages: English
• ISSNs: 0009-9104

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>Accumulating lines of evidence have suggested that regulatory T cells (T<sub>regs</sub>) play a central role in T cell‐mediated immune response and the development of type 1A and fulminant type 1 diabetes. CD4<sup>+</sup>forkhead box protein 3 (FoxP3)<sup>+</sup> T cells are composed of three phenotypically and functionally distinct subpopulations; CD45RA<sup>+</sup>FoxP3<sup>low</sup> resting T<sub>regs</sub> (r‐T<sub>regs</sub>), CD45RA<sup>−</sup>FoxP3<sup>high</sup> activated T<sub>regs</sub> (a‐T<sub>regs</sub>) and CD45RA<sup>−</sup>FoxP3<sup>low</sup> non‐suppressive T cells (non‐T<sub>regs</sub>). We aimed to clarify the frequency of these three subpopulations in CD4<sup>+</sup>FoxP3<sup>+</sup> T cells and the function of a‐T<sub>regs</sub> with reference to subtypes of type 1 diabetes. We examined 20 patients with type 1A diabetes, 15 patients with fulminant type 1 diabetes, 20 patients with type 2 diabetes and 30 healthy control subjects. A flow cytometric analysis in the peripheral blood was performed for the frequency analysis. The suppressive function of a‐T<sub>regs</sub> was assessed by their ability to suppress the proliferation of responder cells in a 1/2:1 co‐culture. A flow cytometric analysis in the peripheral blood demonstrated that the frequency of a‐T<sub>regs</sub> was significantly higher in type 1A diabetes, but not in fulminant type 1 diabetes, than the controls. Further, the proportion of a‐T<sub>regs</sub> among CD4<sup>+</sup>FoxP3<sup>+</sup> T cells was significantly higher in patients with type 1A diabetes with detectable C‐peptide but not in patients with type 1A diabetes without it and with fulminant type 1 diabetes. A proliferation suppression assay showed that a‐T<sub>regs</sub> were functionally impaired both in fulminant type 1 diabetes and in type 1A diabetes. In conclusion, a‐T<sub>regs</sub> were functionally impaired, related to residual insulin‐secreting capacity and may be associated with the development of type 1 diabetes.</p> </abstract>