The CD4+ regulatory T-cells is decreased in adults with latent autoimmune diabetes
Introduction
Type 1 diabetes is a T-cell-mediated autoimmune disease that results in the destruction of the insulin-secreting β-cells [1]. Autoreactive T-cells that recognize islet autoantigens have been identified and are thought to play a direct role in type 1 diabetes immunopathogenesis [2], [3]. But the mechanisms that lead to disease development are not known with certainty.
Recent interest has focused on a feature of tolerance that seems to bridge the central and peripheral processes, namely the CD4+ regulatory T-cell [4]. The CD4+regulatory T-cells that exert their suppressive function in vitro in a contact-dependent manner and preferentially express high levels of CD25 and the forkhead and winged-helix family transcription factor forkhead box P3 (FOXP3). FOXP3 plays crucial role in the development and function of CD4+ regulatory T-cells [5], [6]. The regulatory T-cells have been shown to be defective in patients with type 1 diabetes, multiple sclerosis, rheumatoid arthritis and other autoimmune diseases [7], [8], [9], [10].
The latent autoimmune diabetes in adults (LADA) is a subgroup of type 1 diabetes who, showed preserved β-cell function, initially misclassified as type 2 diabetes [11], [12]. The development of symptoms is insidious and the clinical diabetes becomes overt at the age of 30s or older, and often is maintained in good metabolic control on diet or oral hypoglycemic therapy for up to several years before insulin dependency [13], [14]. So it has been suggested that LADA deviates from classic type 1 diabetes [15]. Until now, LADA remains poorly understood at both a clinical and research level [16].
Our approach was to investigate the pathogenesis of LADA. Thus, we examined the lymphocyte subsets including the CD4+CD25+ T fells and the expression of FOXP3 mRNA in CD4+ T-cell of the patients with LADA.
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Patients and healthy control subjects
We enrolled 60 patients in this study with definite LADA and 30 patients with type 2 diabetes upon informed consent. This work was approved by the Institutional Review Board at the Second Xiangya Hospital. The range of diabetes duration in LADA patients were from 1 month to 8 years, eight recent onset LADA patients included. All patients had no other autoimmune diseases and did not receive any immunomodulatory drugs. Thirty normal healthy donors with no history of autoimmune diseases and
The general characteristics
Table 1 showed general characteristics of all groups. There were matched in age, sex, BMI in three groups. After statistical analysis, LADA patients had higher FBS and HbA1c compared with patients of type 2 diabetes. No significant differences were present in duration of diabetes and FCP levels in the two groups.
The lymphocyte subsets in peripheral blood
The percentage of CD4+CD25+ T-cells was evaluated as a proportion of CD4 T lymphocyte population. They were matched in CD3 T lymphocyte and no CD4 lymphopenia noted in three groups.
In
Discussion
Immune responses need to be constantly regulated—a balancing act that ensures appropriate reactivity to pathogens while preventing the development of an unwanted autoimmune reaction. Recently, this has been shown to be mediated by the CD4+ regulatory T-cells, which are characterized by expression of CD25 (the interleukin-2 (IL-2) receptor α-chain). These cells comprise ∼5–10% of the total population of CD4+ T-cells in mice and are thought to be crucial in the repression of autoimmune disorders
Acknowledgments
This study was supported, in part, by the National Natural Science Foundation of China (39370343) and Hunan Health Bureau Key Research Funds (9736, 2001-Z04). We thank Dr. Bill Hagopian for providing the recombinant hGAD65 plasmid.
We are grateful to all the patients and control subjects who donated blood samples.
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