Diabetes is not prevented by Foxp3-transduced CD4(+)T cells under the IL-12Rbeta2 promoter control.
Our previous studies have shown that Foxp3 under the control of IFN-gamma promoter (IgammaP-Foxp3) converts pathogenic CD4(+)Th1 cells into regulatory T cells (Tregs), which control diabetes in non-obese diabetic (NOD) mice. Here, we tested the other hypothesis that transient expression of Foxp3 as controlled by the transient expression of IL-12Rbeta2 during Th1 cell derivation is sufficient to convert cells to Tregs. Foxp3, under the control of IL-12Rbeta2 promoter (Ibeta2P), was lentivirally transduced into naïve CD4(+)T cells from NOD mice. Ibeta2P-Foxp3-transduced CD4(+)T cells could not effectively suppress the incidence of diabetes when transferred into NOD mice. Furthermore, we found that Ibeta2P-Foxp3-transduced CD4(+)T cells, stimulated by a high dose of autoantigen, did not suppress CD4(+)T cell activation, produce CD4(+)Foxp3(+)Tregs, and up-regulate CTLA4 expression. These results suggest that Ibeta2P cannot mediate Foxp3 to convert pathogenic CD4(+)Th1 cells into Tregs which control diabetes in NOD mice.
Wang
Renxi
R
Department of Molecular Immunology, Institute of Basic Medical Sciences, Taiping Road, No. 27, Beijing 100850, People's Republic of China.
Han
Gencheng
G
Wang
Jianan
J
Song
Lun
L
Chen
Guojiang
G
Xu
Ruonan
R
Wang
Liyan
L
Li
Xia
X
Shen
Beifen
B
Li
Yan
Y
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D016688:Mice, Inbred NOD; D011401:Promoter Regions, Genetic; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014161:Transduction, Genetic
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse