Mechanisms of regulatory T-cell induction by antigen-IgG-transduced splenocytes.
Our previous studies have demonstrated that splenocytes, transduced with glutamate decarboxylate 65 (GAD) and IgG fusion construct, protect non-obese diabetes (NOD) mice from diabetes. However, the mechanism by which this strategy prevents diabetes is not well understood. Here, we found that CD4(+)Foxp3(+)Treg cells, in vitro induced by GAD-IgG-transduced splenocytes, after transfer, were responsible for prevention of diabetes in NOD mice. Further studies suggested that GAD-IgG-transduced B cells could secrete high level of TGF-beta and stimulated CD4(+)T cells to secrete high level of IFN-gamma. Finally, we found that when TGF-beta and/or IFN-gamma were blocked, CD4(+)Foxp3(-)T cells were not converted into CD4(+)Foxp3(+)Treg cells. The results suggest that GAD-IgG-transduced B cells via TGF-beta and IFN-gamma in vitro induce the CD4(+)Foxp3(+)Treg cells which are responsible for prevention of diabetes in NOD mice by GAD-IgG-gene transfer.
Wang
R
R
Department of Molecular Immunology, Institute of Basic Medical Sciences, Beijing, China.
Song
L
L
Han
G
G
Wang
J
J
Chen
G
G
Xu
R
R
Yu
M
M
Qian
J
J
Shen
B
B
Li
Y
Y
D000818:Animals; D000941:Antigens / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D017690:Cell Transplantation; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D005968:Glutamate Decarboxylase / Q000235:genetics* / Q000276:immunology; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000235:genetics* / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014161:Transduction, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism
D000941:Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma; D005968:Glutamate Decarboxylase