|
Robby Kumar |
Department of Biochemistry, SSR Medical College, Mauritius |
*Corresponding authors: |
Robby Kumar
Department of Biochemistry
SSR Medical College, Mauritius
E-mail: kumarrobby@gmail.com |
|
|
Received May 09, 2012; Published July 26, 2012 |
|
Citation: Kumar R (2012) Prevention of Type 1 Diabetes by Regulation of the Immune System. 1: 154. doi:10.4172/scientificreports.154 |
|
Copyright: © 2012 Kumar R. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
|
Abstract |
|
Immune mediated beta cell destruction is one of the major causes for type1 diabetes mellitus, which makes immune system a primary target for intervention for prevention of type1 diabetes. This review is done to know the immunological interventions for T1DM prevention viz immunosuppressive agents, Antigen Specific Immunotherapy, Anti-CD3 Antibodies and Anti CD20 antibodies. |
|
Keywords |
|
Diabetes mellitus; Immunosuppressive agents; Anti CD3 Antibodies |
|
Introduction |
|
Diabetes mellitus is a metabolic disorder characterized by hyperglycemia due to absolute and relative insulin deficiency. Type 1 diabetes mellitus also known as insulin dependent diabetes mellitus accounts for 5-10% of all causes of the syndrome, is a T-cell–mediated autoimmune disease that begins, in many cases, three to five years before the onset of clinical symptoms, continues after diagnosis, and can recur even after islet transplantation.1-3 Theeffector mechanisms which is responsible for the destruction of beta cells involves the action of cytotoxic T cells as well as soluble T-cell products [1,2]. |
|
Immunological Intervention for Treatment of Diabetes Mellitus Type 1 Immunosuppressive Agent |
|
These are the agents which decreases the destruction of pancreatic beta cells. One of the example for the immunosuppressive agent is Cyclosporin A which blocks cytokine production by all T cells thus limiting production of the T-cell, it also prevents the secretion of cytokines, which is animportant direct mediators of beta cell destruction, these includes Interferon C (IFN-c) and Tumor Necrosis Factor a (TNF-a) [3,4]. Cyclosporine A, hasbeen reported to decrease destruction of beta cells [5]. Although Cyclosporin A targeted cytokine production, other broadspectrum immunosuppressive regimens also may be effective in preventingthe loss of insulin production [6]. These immunosuppressive agents are nephrotoxic and have other side effects making it highly inappropriate for long term uses [6]. |
|
Antigen Specific Immunothreapy |
|
These strategies are based on the factthat a response to antigen is affected by many factors which include the antigenic signal strength, costimulation, and the cytokine environment. Therefore, by modulating these parameters, it is possible to divert pathogenic responses of the antigens into a protective, nonpathogenic response [4,6]. In addition to modifying the strength of the T-cell receptor signal with altered ligands or adjuvants, the prevention of antigen can be altered [7,8,9]. By this way type 1 Diabetes Mellitus can be prevented by inducing immune regulation to the administrated antigen. |
|
Anti-Cd3 Antibodies |
|
Anti CD 3 molecules contain FcR- binding portion which is responsible for T-Cell activation signals and other effects of T-Cells, thus by eliminating FcR binding portion of Anti CD3 molecule type 1 diabetes mellitus can be prevented. It has been reported that non- FcR binding antibody induces previously activated T-Cells but naïve cells were unaffected. Also, the other inhibitory effects were limited to the previously activated T-helper cells- which are involved and are present in pancreas of subjects with type1 diabetes mellitus. Anti CD 3 antibody molecule may induce tolerance to autoimmune destruction of pancreatic beta cells preventing diabetes mellitus type1. The non FcR binding antibodies activates signal to T cells resulting in release of Interleukin 10 (IL 10). The conventional Anti CD3 Antibodies release IFN-c [10-13]. |
|
An Anti-Cd20 Antibody |
|
These molecules inhibits B cells, it has been reported that anti CD 20 Antibodies also provoke C-peptide responses. Through their action prevents type1 diabetes but long term action have not been studied in detail [4]. |
|
|
References |
|
- Atkinson MA, Eisenbarth GS (2001) Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet 358: 221-229.
- Herold KC, Hagopian W, Auger JA, Poumian-Ruiz E, Taylor L, et al. (2002) Anti-Cd3 Monoclonal Antibody in New-Onset Type 1 Diabetes Mellitus. N Engl J Med 346: 1692-1698.
- Herold KC, Lancki DW, Moldwin RL, Fitch F (1986) Immunosuppressive effects of cyclosporin A on cloned T cells. J Immunol 136: 1315-1321.
- Rabinovitch A (1998) An update on cytokines in the pathogenesis of insulin-dependent diabetes mellitus. Diabetes Metab Rev 14: 129-151.
- Bluestone JA, Herold K, Eisenbarth G (2010) Genetics, pathogenesis and clinical interventions in type?1 diabetes. Nature 464:1293-1300.
- Herold KC (2004) Treatment of type 1 diabetes mellitus to preserve insulin secretion. Endocrinol Metab Clin North Am 33: 93-111.
- Steptoe RJ, Ritchie JM, Harrison LC (2003) Transfer of hematopoietic stem cells encoding autoantigen prevents autoimmune diabetes. J Clin Invest 111: 1357-1363.
- Tian J, Atkinson MA, Clare-Salzler M, Herschenfeld A, Forsthuber T, et al. (1996) Nasal administration of glutamate decarboxylase (GAD65) peptides induces Th2 responses and prevents murine insulindependent diabetes. J Exp Med 183: 1561-1567.
- Hänninen A, Harrison LC (2000) Gamma delta T cells as mediators of mucosal tolerance: the autoimmune diabetes model. Immunol Rev 173: 109-119.
- Smith JA, Tso JY, Clark MR, Cole MS, Bluestone JA (1997) Nonmitogenic anti-CD3 monoclonal antibodies deliver a partial T cell receptor signal and induce clonal anergy. J Exp Med 185: 1413-1422.
- Smith JA, Tang Q, Bluestone JA (1998) Partial TCR signals delivered by FcR-nonbinding anti- CD3 monoclonal antibodies differentially regulate individual Th subsets. J Immunol 160: 4841-4849.
- Smith JA, Bluestone JA (1997) T cell inactivation and cytokine deviation promoted by anti-CD3 mAbs. Curr Opin Immunol 9: 648-654.
- Herold KC, Burton JB, Francois F, Poumian-Ruiz E, Glandt M, et al. (2003) Activation of human T cells by FcR nonbinding anti-CD3 mAb, hOKT3gamma1(Ala-Ala). J Clin Invest 111: 409-418.
|
|
|