title: Less is more: the detrimental consequences of immunosuppressive therapy in the treatment of type-1 diabetes.
abstract: The prevalent current approach to type 1 diabetes (T1D) is the abrogation of pathogenic potential by immunosuppressive therapy, an intuitive approach aiming to slow down disease progression by the reduction of pathogenic burden. In spite of promising initial results in rodent models, there has been little efficacy of most lymphoreductive strategies in human subjects. Our analysis suggests that lymphopenia is the common denominator of ineffective immunosuppressive therapies: Immune rebound from lymphopenia is associated per se with increased susceptibility to immune reactivity, including relapse of autoimmunity. In addition, immune homeostasis and self-tolerance are not restored. These considerations raise the following question: What is the allowed degree of immunosuppressive therapy that does not elicit recurrent autoimmunity. More effective therapeutic strategies include targeted deletion of pathogenic cells, preferably in the pancreatic islets and regional lymphatics using selective T cell activation markers, re-education and remodeling of effector responses.
authors: a Frankel Laboratory, Department of Pediatric Hematology Oncology , Schneider Children's Medical Center of Israel , Petach Tikva , Israel.
authors: Nadir
authors: N
authors: Askenasy
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D017690:Cell Transplantation; D059248:Chemoradiotherapy / Q000379:methods; D000068456:Clinical Studies as Topic; D003131:Combined Modality Therapy; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000628:therapy*; D004195:Disease Models, Animal; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008212:Lymphocyte Depletion; D051379:Mice; D011379:Prognosis; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents
keywords: T cell depletion; immunomodulation; immunosuppressive therapy; lymphopenia; type 1 diabetes