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


CONCLUSIONS
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.
Ugrasbul
Figen
F
Section of Endocrinology & Diabetes, Children's Mercy Hospital, University of Missouri Kansas City School of Medicine, Kansas City, MO 64108, USA. fugrasbul@cmh.edu
Moore
Wayne V
WV
Tong
Pei Ying
PY
Kover
Karen L
KL
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology / Q000517:prevention & control*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010179:Pancreas / Q000473:pathology; D051381:Rats; D011913:Rats, Inbred BB
D000906:Antibodies; D053645:Interleukin-2 Receptor alpha Subunit; D009173:Mycophenolic Acid