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  • Review Article
  • Published:

Immune therapy for type 1 diabetes mellitus—what is unique about anti-CD3 antibodies?

Nature Reviews Endocrinology volume 6, pages 149–157 (2010)Cite this article

Subjects

Abstract

Type 1 diabetes mellitus (T1DM) is a prototypic organ-specific autoimmune disease that results from selective destruction of insulin-secreting β-cells by immune-mediated inflammation (insulitis), that is, the infiltration of pancreatic islets by autoreactive CD4+ and CD8+ T lymphocytes. Current treatment is substitutive—chronic use of exogenous insulin—which, in spite of considerable advances, is still associated with constraints and lack of effectiveness over the long-term in relation to the prevention of vascular and neurological complications. Finding a cure for T1DM is an important medical health challenge, as the disease's incidence is steadily increasing in industrialized countries and projections of future prevalence are alarming. Crucially, as T1DM mainly affects children and young adults, any candidate immune therapy must be safe and avoid chronic use of immunosuppressants that promote sustained depression of immune responses. The ideal approach would, therefore, involve induction or, in the case of established T1DM, restoration of immune tolerance to target autoantigens. This Review presents, in particular, two strategies that are still in clinical development but hold great promise. These strategies are focused on the use of candidate autoantigens and anti-CD3 monoclonal antibodies.

Key Points

  • Type 1 diabetes mellitus (T1DM) is a prototypic autoimmune disease whose pathophysiology involves autoantigen-presenting cells (dendritic cells, macrophages and B lymphocytes), T lymphocytes and target insulin-secreting β cells

  • Immune destruction of β cells in humans starts months to years before the advent of overt hyperglycemia

  • The incidence of T1DM has steadily increased in developed countries over the past few decades; prevalence in children <15 years is predicted to increase by 70% between 2005 and 2020

  • Given the autoimmune origin of T1DM, immune intervention is the only option to find a real cure

  • The possibility exists to reverse T1DM once hyperglycemia is established, as β cells have not all been destroyed

  • Chronic immunosuppression may be effective, but is not the way to go because of the potential long-term adverse effects

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Figure 1: Biological effects of anti-CD3 antibodies on T cells.
Figure 2: Local interactions before and after anti-CD3 antibody treatment.

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  1. Université Paris Descartes, INSERM U1013, Hôpital Necker Enfants Malades, 161 Rue de Sèvres, Paris, 75015, France

    Lucienne Chatenoud

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Chatenoud, L. Immune therapy for type 1 diabetes mellitus—what is unique about anti-CD3 antibodies?. Nat Rev Endocrinol 6, 149–157 (2010). https://doi.org/10.1038/nrendo.2009.275

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