GAD-IgG-inducing CD4+Foxp3+Treg cells suppressing diabetes are involved in the increasing ratio of CD80+:CD86+ CELLS in NOD mice.
BACKGROUND
Our previous studies have demonstrated that GAD-IgG-transduced splenocytes protect non-obese diabetic (NOD) mice from diabetes by in vitro-inducing CD4(+)Foxp3(+)Treg cells. However, the underlying mechanisms by which CD4(+)Foxp3(+)Treg cells suppress diabetes remain unclear.


METHODS
Seven-week-old female NOD mice were intravenously injected with GAD-IgG-transduced splenocytes. The ratio of CD80(+):CD86(+) cells in splenocytes was analyzed by flow cytometry. The effect of the ratio of CD80(+):CD86(+) cells on tolerance, diabetes prevention, and Foxp3 expression in GAD-IgG-treated NOD mice was tested by in vitro proliferation, in vivo antibody block, and semi-quantified RT-PCR, respectively.


RESULTS
We found that the ratio of CD80(+):CD86(+) cells increased in GAD-IgG-treated NOD mice. After CD4(+)Treg cells were depleted from GAD-IgG-transduced splenocytes before transfer, the ratio of CD80(+):CD86(+) cells decreased in NOD mice recipients. The increasing ratio of CD80(+):CD86(+) cells was positively associated with tolerance, diabetes prevention, and the high level of Foxp3 in GAD-IgG-treated NOD mice.


CONCLUSIONS
These findings suggest that the high ratio of CD80(+):CD86(+) cells is required for the suppressive function of GAD-IgG-inducing CD4(+)Foxp3(+)Treg cells in NOD mice.
Wang
Renxi
R
Department of Molecular Immunology, Institute of Basic Medical Sciences, Beijing, PR China.
Han
Gencheng
G
Wang
Jianan
J
Song
Lun
L
Chen
Guojiang
G
Xu
Ruonan
R
Zhang
Chunmei
C
Yu
Ming
M
Qian
Jiahua
J
Shen
Beifen
B
Li
Yan
Y
D000818:Animals; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen / Q000276:immunology; D003920:Diabetes Mellitus / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology*; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism*; D007108:Immune Tolerance / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D015854:Up-Regulation
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007074:Immunoglobulin G; D010446:Peptide Fragments; D005968:Glutamate Decarboxylase