An immunohistochemical study on the distribution and frequency of T regulatory cells in pancreatic islets of NOD mice during various stages of spontaneous and cyclophosphamide-accelerated diabetes.
OBJECTIVE
To determine if there is an abrupt change in the frequency of intraislet T regulatory (Treg) cells in female nonobese diabetic (NOD) mice preceding and following spontaneous diabetes and during cyclophosphamide-accelerated disease.


METHODS
The frequency of intraislet CD4-positive Treg cells was analyzed between days 21 and 250, at onset, and at 1, 2, and 3 weeks of diabetes by dual-label immunohistochemistry. Tissues were also analyzed between days 0 and 14 after injection of cyclophosphamide or diluent.


RESULTS
In the spontaneous group, intraislet Treg cells were first observed on day 30 in CD4 T cells and increased from day 45. There was no statistical difference in the frequency of Treg cells in nondiabetic NOD mice on days 45, 60, and 90. A sustained frequency at and after 1, 2, and 3 weeks of diabetes was also observed. In the cyclophosphamide group, there was a sharp decline in the frequency of Treg cells on day 4, which remained lower on day 7 but increased by days 11 and 14.


CONCLUSIONS
During spontaneous diabetes and after onset, the frequency of intraislet CD4-positive Treg cells remains unchanged. They may possess diminished immunoregulatory function and thus unable to counteract the increasing tempo of immune-mediated beta-cell destruction.
Kaur
Sarbjot
S
School of Biological Sciences, The University of Auckland, Auckland, New Zealand.
Tan
Wan Ling
WL
Soo
Camelia
C
Cheung
Carlos Chun Ho
CC
Stewart
Joanna
J
Reddy
Shiva
S
D000818:Animals; D003520:Cyclophosphamide / Q000633:toxicity*; D003920:Diabetes Mellitus / Q000139:chemically induced / Q000276:immunology*; D005260:Female; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
D003520:Cyclophosphamide