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KMID : 0381120080300060555
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Genes and Genomics
2008 Volume.30 No. 6 p.555 ~ p.561
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The Effect of CD28 Stimulation on in vitro Generation of Regulatory T Cells with IL2 and TGFβ
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Oh Kyu-Heon
Jeon Sung-Ho
Hong Seok-Mann
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Abstract
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Regulatory T cells (Tregs) play an important role in regulating immune responses and maintaining peripheral immune tolerance. In vitro Treg cells generated with IL2 and TGFβ have been used to address immunoregulatory functions of these cells. Although emerging evidences suggest that CD28 signaling is critical for development and functions of Treg cells, the role of CD28 signaling on in vitro differentiated Tregs remains unclear. Therefore, we decided to test whether CD28 stimulation during in vitro culture of Treg cells has any significant influence on differentiation and functions of these cells. We found that CD28 stimulation of naive CD4+ T cells in the presence of IL2 plus TGFβ could produce less numbers of Foxp3+ Treg cells compared to the unstimulated group. However, Treg population generated with CD28 stimulation showed greater suppressive activities than the control Tregs. Next, the expression level of immunosuppressive molecules such as CTLA4 and GITR were examined on the in vitro Treg cells. We found that CD28-stimulated Treg cells during their differentiation induced higher levels of CTLA4 and comparable levels of GITR expression, which may explain how less Foxp3+ Treg population could provide better suppression than the control group containing more Foxp3+ Treg cells. These findings were confirmed by experiments in which dendritic cells were added during in vitro culture of Treg cells instead of anti-CD28 mAbs. Taken together, our studies suggest not only that CD28 stimulation has a negative influence on the expression of Foxp3 gene but also that Foxp3 expression does not always correlate with the extent of suppressive ability.
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KEYWORD
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regulatory T cellsl, CD28, dendritic cells, Foxp3, CTLA4
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