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Open Journal of Biology and Biochemistry

ISSN: 2227-7021
Volume 2, 2017


Open Journal of Biology and Biochemistry, 2012, 1-2 [Research Article]

Patients with Type 1 Diabetes Display Selective Defect in Antigen Receptor Mediated T Cell Apoptosis

Sundararajan Jayaraman1, 2*, Selvakumar Balasingh1, Jesus Exposito1, Geston Ponte1, David Baidal1, Pablo Cure1, Muhammad Hafiz1, Luigi Meneghini1, Tatiana Froud1, Rodolfo Alejandro1, Camillo Ricordi1
1 Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA
2 Department of Surgery, University of Illinois at Chicago, Chicago, IL, USA

Corresponding Author & Address:

Sundararajan Jayaraman
Dept. of Surgery, University of Illinois at Chicago, College of Medicine, 909 South Wolcott Avenue, Chicago, IL 60612, USA, Phone: 312-355-1470; Fax: 312-996-7193; Email: anue2468@uic.edu

Article History:
Published: 3rd July, 2012   Accepted: 3rd July, 2012
Received: 27th May, 2012      

© Jayaraman et al.; licensee Ross Science Publishers

ROSS Open Access articles will be distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided that the original work will always be cited properly.

Keywords: Apoptosis, caspases, Fas, mitochondria, T cell receptor, type 1 diabetes

Abstract:

Type 1 diabetes is an autoimmune disease in which insulin-producing beta cells are destroyed by auto-reactive T lymphocytes. Studies in mice indicate that incomplete deletion of self-reactive T-cells and compromised peripheral tolerance mechanisms can contribute to the manifestation of autoimmune diabetes. In patients with type 1 diabetes, defects in T regulatory cell numbers and function have been previously reported. In this study, we have ascertained the integrity of activation-induced cell death, a mechanism of peripheral T cell tolerance, in long-standing type 1 diabetes patients. Activation of peripheral blood derived T cells from non-diabetic individuals with a T cell mitogen and interleukin-2 rendered them susceptible to subsequent T-cell receptor/CD3-mediated apoptosis, as indicated by the dissipation of the mitochondrial membrane potential and activation of intracellular caspases. In contrast, similarly activated T lymphocytes from type 1 diabetes patients failed to undergo apoptosis when challenged with a bacterial superantigen or anti-CD3 antibody. Supplementation of T cell cultures with interleukin-4 or interleukin-18 failed to restore self-tolerance. However, both the expression of the Fas receptor and its ability to transduce apoptotic signal were comparable in T cells of type 1 diabetes patients and controls. Additionally, no marked difference in the T cell subsets was observed between controls and diabetes patients under all activation conditions analyzed. These data suggest that the abnormality in T-cell receptor-mediated apoptosis is cell autonomous in long-standing type 1 diabetes patients, which in addition to other defective peripheral tolerance mechanisms, likely to contribute to the manifestation of autoimmune diabetes.



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