Skip to main content
Article thumbnail
Location of Repository

Rapamycin Prevents and Breaks the Anti-CD3–Induced Tolerance in NOD Mice

By Andrea Valle, Tatiana Jofra, Angela Stabilini, Mark Atkinson, Maria-Grazia Roncarolo and Manuela Battaglia
Topics: Brief Report
Publisher: American Diabetes Association
OAI identifier:
Provided by: PubMed Central

Suggested articles


  1. (2006). Anti-CD3 and nasal proinsulin combination therapy enhances remission from recent-onset autoimmune diabetes by inducing Tregs.
  2. (2008). Bernal-Mizrachi E: Disruption of Tsc2 in pancreatic beta cells induces beta cell mass expansion and improved glucose tolerance in a TORC1-dependent manner.
  3. (2005). Bluestone JA: A single course of anti-CD3 monoclonal antibody hOKT3 results in improvement in C-peptide responses and clinical parameters for at least 2 years after onset of type 1 diabetes. Diabetes 54:1763–1769,
  4. (2007). Bluestone JA: CD3-specific antibodies: a portal to the treatment of autoimmunity. Nat Rev Immunol 7:622–632,
  5. (2008). Bluestone JA: Central role of defective interleukin-2 production in the triggering of islet autoimmune destruction. Immunity 28:687–697,
  6. (2005). Bluestone JA: The NOD mouse: a model of immune dysregulation. Annu Rev Immunol 23:447–485,
  7. (2003). CD3-specific antibody-induced active tolerance: from bench to bedside. Nat Rev Immunol 3:123–132,
  8. (2005). Chatenoud L: Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes.
  9. (2003). Chatenoud L: TGF-beta-dependent mechanisms mediate restoration of self-tolerance induced by antibodies to CD3 in overt autoimmune diabetes. Nat Med 9:1202–1208,
  10. (2002). Combination therapy with sirolimus and interleukin-2 prevents spontaneous and recurrent autoimmune diabetes in NOD mice. Diabetes 51:638– 645,
  11. (2006). Contag CH, Negrin RS: Inhibition of CD4CD25 regulatory T-cell function by calcineurin-dependent interleukin-2 production. Blood 108:390–399,
  12. (2008). de Casteele M: Akt activation protects pancreatic beta cells from AMPK-mediated death through stimulation of mTOR. Biochem Pharmacol 75:1981–1993,
  13. (2009). G: mTOR inhibition by rapamycin prevents -cell adaptation to hyperglycemia and exacerbates the metabolic state in type 2 diabetes. Diabetes 57:945–957,
  14. (2006). IJ: Rapamycin does not induce anergy but inhibits expansion and differentiation of alloreactive human T cells. Transplantation 81:445–454,
  15. (1994). JF: Anti-CD3 antibody induces long-term remission of overt autoimmunity in nonobese diabetic mice.
  16. (1997). JF: CD3 antibody-induced dominant self tolerance in overtly diabetic NOD mice.
  17. (2007). KC: Autoimmunity and beta cell regeneration in mouse and human type 1 diabetes: the peace is not enough.
  18. (2007). KC: Exendin-4 improves reversal of diabetes in NOD mice treated with anti-CD3 monoclonal antibody by enhancing recovery of beta-cells. Endocrinology 148:5136–5144,
  19. (2005). Kreuwel HT: A comprehensive review of interventions in the NOD mouse and implications for translation. Immunity 23:115–126,
  20. (2007). Moving towards efficient therapies in type 1 diabetes: to combine or not to combine? Autoimmun Rev 6:315–322,
  21. (2008). Rapamycin impairs beta-cell proliferation in vivo. Transplant Proc 40:436–437,
  22. (2007). Recovery from diabetes in mice by beta cell regeneration.
  23. (2008). Regulatory T cells and immune tolerance. Cell 133:775–787,
  24. (2007). Remuzzi G: Regulatory T cells and T cell depletion: role of immunosuppressive drugs.
  25. (2006). Roncarolo MG: Induction of tolerance
  26. (2006). Roncarolo MG: Rapamycin and interleukin-10 treatment induces T regulatory type 1 cells that mediate antigen-specific transplantation tolerance. Diabetes 55:40–49,
  27. (2006). Roncarolo MG: Rapamycin promotes expansion of functional CD4CD25FOXP3 regulatory T cells of both healthy subjects and type 1 diabetic patients.
  28. (2005). Roncarolo MG: Rapamycin selectively expands CD4CD25FoxP3 regulatory T cells. Blood 105:4743–4748,
  29. (2007). TB: Contrasting effects of cyclosporine and rapamycin in de novo generation of alloantigenspecific regulatory T cells.
  30. (2004). The pleiotropic effects of mTor inhibitors.

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.