%0 Journal Article
%T Immunotherapy with Tolerogenic Dendritic Cells Alone or in Combination with Rapamycin Does Not Reverse Diabetes in NOD Mice
%A Irma Pujol-Autonell
%A Rosa M. Ampudia
%A Pau Monge
%A Anna M. Lucas
%A Jorge Carrascal
%A Joan Verdaguer
%A Marta Vives-Pi
%J ISRN Endocrinology
%D 2013
%R 10.1155/2013/346987
%X Type 1 diabetes is a metabolic disease caused by autoimmunity towards ¦Â-cells. Different strategies have been developed to restore ¦Â-cell function and to reestablish immune tolerance to prevent and cure the disease. Currently, there is no effective treatment strategy to restore endogenous insulin secretion in patients with type 1 diabetes. This study aims to restore insulin secretion in diabetic mice with experimental antigen-specific immunotherapy alone or in combination with rapamycin, a compound well known for its immunomodulatory effect. Nonobese diabetic (NOD) mice develop spontaneous type 1 diabetes after 12 weeks of age. Autologous tolerogenic dendritic cells¡ªconsisting in dendritic cells pulsed with islet apoptotic cells¡ªwere administered to diabetic NOD mice alone or in combination with rapamycin. The ability of this therapy to revert type 1 diabetes was determined by assessing the insulitis score and by measuring both blood glucose levels and C-peptide concentration. Our findings indicate that tolerogenic dendritic cells alone or in combination with rapamycin do not ameliorate diabetes in NOD mice. These results suggest that alternative strategies may be considered for the cure of type 1 diabetes. 1. Introduction Type 1 diabetes (T1D) results from the autoimmune destruction of insulin-producing ¦Â-cells in the pancreatic islets of Langerhans [1]. The prevalence of this disease, its complications, and the lack of effective curative and preventive strategies call for a significant effort to find means to restore the tolerance to ¦Â-cells as the best way to control this disease. Recently, we reported a new experimental immunotherapy protocol based on the use of dendritic cells (DCs) loaded with islet apoptotic cells. This protocol clearly reduces T1D incidence and insulitis in non-obese diabetic mice (NOD) [2]. The NOD mouse strain is an excellent model for autoimmune diabetes. A limited number of treatments were demonstrated to revert established diabetes in NOD mice [3, 4]. Given the preventive effectiveness of DCs loaded with islet apoptotic cells, we tested whether this immunotherapy is able to reverse diabetes. To improve this treatment, we also combined tolerogenic DCs with rapamycin, an immunosuppressant that inhibits the response to IL-2 and thereby blocks the activation of T and B lymphocytes. Rapamycin, a noncalcineurin-based inhibitor, was used to prevent acute graft rejection following allogeneic transplantation [5] and helps to expand T regs [6]. Therefore, we hypothesized that the administration of rapamycin prior to immunotherapy
%U http://www.hindawi.com/journals/isrn.endocrinology/2013/346987/