title: Targeted immune interventions for type 1 diabetes: not as easy as it looks!
abstract: OBJECTIVE
  Although insulin is lifesaving and sustaining for those with type 1 diabetes (T1D), curing the disease will be much more complex than simple replacement of this hormone. T1D is an autoimmune disease orchestrated by T cells, and includes many arms of the immune response. Tremendous effort has gone into understanding its underlying immune, genetic, and environmental causes, and this progress has led to immunologically based clinical trials in T1D. This review will focus primarily on the clinical trials of the past decade that have attempted to translate these fundamental findings.
  
  
  RESULTS
  It is known that powerful, nonspecific immune suppressants can temporarily slow the course of newly diagnosed T1D, yet are too toxic for long-term use, especially in children. Recent clinical trials to reverse T1D have used newly developed therapies that target specific components of the immune process believed to be involved with T1D. Although well justified and designed, no recent approach has resulted in clinical remission and few have had any effect on disease course.
  
  
  CONCLUSIONS
  Advances in our fundamental understanding of how the human diabetes immune response is activated and regulated coupled with lessons that have been learnt from the most recent era of completed trials are guiding us toward the development of more effective, multipronged therapies to ablate diabetes autoimmunity, restore immune tolerance, preserve β cells, and, ultimately, improve the lives of patients with T1D.
authors.affiliation: aIndiana University School of Medicine and Riley Hospital for Children at IU Health, Indianapolis, Indiana bImmune Tolerance Network, San Francisco, California, USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Rigby
authors.forename: Mario R
authors.initials: MR
authors.lastname: Ehlers
mesh_terms: D015551:Autoimmunity; D002986:Clinical Trials as Topic; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007167:Immunotherapy / Q000639:trends; D007328:Insulin; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000187:drug effects / Q000276:immunology*
chemical_list: D007328:Insulin; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7