Prevention of diabetes: effect of mycophenolate mofetil and anti-CD25 on onset of diabetes in the DRBB rat

Pediatr Diabetes. 2008 Dec;9(6):596-601. doi: 10.1111/j.1399-5448.2008.00417.x. Epub 2008 May 21.


Background: Anti-CD25 and mycophenolate mofetil (MMF) treatment of patients with new-onset diabetes is currently being tested as one of the trials in TrialNet. We tested the effectiveness of MMF and anti-CD25 in preventing autoimmune diabetes in the diabetes-resistant biobreeding (DRBB) rat.

Methods: Autoimmune diabetes in the DRBB rat was induced with a Treg cell depletion regimen starting at 24-26 d of age. Treatment was started on the first day of the depletion regimen in the following groups: (i) control (vehicle); (ii) MMF 25 mg/kg/d intramuscularly daily for 8 wk; (iii) anti-CD25 0.8 mg/kg/d intraperitoneally 5 d/wk for 3 wk; and (iv) combination of MMF and anti-CD25. In a second set of experiments, treatments were started on day 5 of the depletion regimen (delayed treatment) with groups 1, 3, and 4. Rats that had diabetes-free survival for at least 30 d after the treatment was stopped underwent a second Treg depletion (redepletion).

Results: In each of the three treatment groups (n = 10/group), onset of diabetes was delayed or prevented in 20, 40 and 80% in groups 2, 3, and 4, respectively. After redepletion, diabetes-free survival was unchanged in group 2 and decreased to 10 and 30% in groups 3 and 4, respectively. With delayed treatment, groups 3 and 4 had 33 and 50% diabetes-free survival that decreased to 0 and 33% after redepletion.

Summary: MMF and anti-CD25 alone or in combination are effective in delaying and preventing diabetes in the DRBB rat especially if treatment is started before stimulation and expansion of the autoreactive T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / therapeutic use*
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 1 / prevention & control*
  • Interleukin-2 Receptor alpha Subunit / immunology*
  • Male
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / therapeutic use
  • Pancreas / pathology
  • Rats
  • Rats, Inbred BB


  • Antibodies
  • Interleukin-2 Receptor alpha Subunit
  • Mycophenolic Acid