A Possible Role in Immune Response Modulation after Autologus Bone Marrow Stem Cell Transplantation in Type 1 DM

Abstract

Summary T ype 1 diabetes is an autoimmune disease and results from T cell-mediated destruction of insulin-producing pancreatic beta cells. Patients at onset of type 1 diabetes usually have limited beta cell mass and depend on exogenous insulin treatment. The development of new therapies to control T cell autoimmunity and to preserve the remaining beta cell function will be of great significance in managing patients with type 1 diabetes. Autologous hematopoietic stem cell transplantation (AHSCT) has been tested for the treatment of patients with new onset of type 1 diabetes. This therapeutic strategy can result in exogenous insulin independence by destroying pathogenic memory T cells and preserving the remaining beta cell function. Type I autoimmune diabetes develops when one or another immunoregulatory mechanism fails, allowing autoreactive T-cells directed against beta cells to become activated and to expand clonally, starting a cascade of immune/inflammatory processes in the islets (insulitis), causing beta cell destruction. The cytokine profile of T-helper cells is crucial to the development of an effective immune response. Th-1 cells secrete IL-2, IFN-γ and tumor necrosis factor beta (TNF-β) which may cause diabetes in different ways. These mediators may stimulate immune inflammatory responses such as the activation of cytotoxic T-cells. This, in turn, may lead to destruction of pancreatic β-cells and activation of macrophages leading to the secretion of proinflammatory cytokines such as IL-1, TNF-α, IFN-γ and free oxygen or nitrogen radicals which are cytotoxic to beta cells. On the other hand, Th-2 cells secrete cytokines such as IL-4 and IL-10 which may be protective for beta cells. IL-4 is the primary cytokine of the Th-2 pathway, Along with its ability to drive T-helper cells to a Th-2 phenotype, IL-4 also possesses strong down regulatory properties with respect to Th-1 cells not excluding autoreactive Th-1 cells. The expression of IL-4 in the target organ significantly reduced the diabetogenic potential of islet-specific T-cells. These findings have led to the development of the hypothesis that prevention of type I diabetes can beachieved by inhibition of Th-1 reactions and stimulation of Th-2 reactions. Aim of this study is to evaluate the possible role of autologus bone marrow transplantation done for cases of type 1 DM in modulating the immune response from T helper 1 to T helper 2. This study is conducted on 10 patients with auto immune type 1 diabetes mellitus (Ain Shams University Hospitals in The Pancreatic Islet Transplantation and diabetes Research Unit) selected according to inclusion and exclusion criteria and sign a written consent. In present study, the mean of fasting blood sugar highly significantly decreased after 3 and 6 months following AHSCT (167.6+34.3), (152.1+31.9) respectively, also the mean of post