DOI: 10.1084/jem.20011629. In Vitro Generation of Interleukin 10–producing Regulatory CD4+ T Cells Is Induced by Immunosuppressive Drugs and Inhibited by T Helper Type 1 (Th1)

In Vitro Generation of Interleukin 10–producing Regulatory CD4+ T Cells Is Induced by Immunosuppressive Drugs and Inhibited by T Helper Type 1 (Th1)– and Th2-inducing Cytokines

10.1084/jem.20011629

Crossref journal-article

Rockefeller University Press

The Journal of Experimental Medicine (291)

Abstract

We show that a combination of the immunosuppressive drugs, vitamin D3 and Dexamethasone, induced human and mouse naive CD4+ T cells to differentiate in vitro into regulatory T cells. In contrast to the previously described in vitro derived CD4+ T cells, these cells produced only interleukin (IL)-10, but no IL-5 and interferon (IFN)-γ, and furthermore retained strong proliferative capacity. The development of these IL-10–producing cells was enhanced by neutralization of the T helper type 1 (Th1)- and Th2–inducing cytokines IL-4, IL-12, and IFN-γ. These immunosuppressive drugs also induced the development of IL-10–producing T cells in the absence of antigen-presenting cells, with IL-10 acting as a positive autocrine factor for these T cells. Furthermore, nuclear factor (NF)-κB and activator protein (AP)-1 activities were inhibited in the IL-10–producing cells described here as well as key transcription factors involved in Th1 and Th2 subset differentiation. The regulatory function of these in vitro generated IL-10–producing T cells was demonstrated by their ability to prevent central nervous system inflammation, when targeted to the site of inflammation, and this function was shown to be IL-10 dependent. Generating homogeneous populations of IL-10–producing T cells in vitro will thus facilitate the use of regulatory T cells in immunotherapy.

Bibliography

Barrat, F. J., Cua, D. J., Boonstra, A., Richards, D. F., Crain, C., Savelkoul, H. F., de Waal-Malefyt, R., Coffman, R. L., Hawrylowicz, C. M., & OâGarra, A. (2002). In Vitro Generation of Interleukin 10âproducing Regulatory CD4+ T Cells Is Induced by Immunosuppressive Drugs and Inhibited by T Helper Type 1 (Th1)â and Th2-inducing Cytokines. The Journal of Experimental Medicine, 195(5), 603â616.

Authors 10

Franck J. Barrat (first)
Daniel J. Cua (additional)
André Boonstra (additional)
David F. Richards (additional)
Chad Crain (additional)
Huub F. Savelkoul (additional)
René de Waal-Malefyt (additional)
Robert L. Coffman (additional)
Catherine M. Hawrylowicz (additional)
Anne O'Garra (additional)

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Dates

Type	When
Created	23 years ago (July 26, 2002, 12:48 p.m.)
Deposited	2 years, 1 month ago (July 25, 2023, 7:31 a.m.)
Indexed	17 minutes ago (Aug. 25, 2025, 10:19 p.m.)
Issued	23 years, 5 months ago (March 4, 2002)
Published	23 years, 5 months ago (March 4, 2002)
Published Online	23 years, 5 months ago (March 4, 2002)
Published Print	23 years, 5 months ago (March 4, 2002)

Funders 0

None

BibTeX

@article{Barrat_2002, title={In Vitro Generation of Interleukin 10–producing Regulatory CD4+ T Cells Is Induced by Immunosuppressive Drugs and Inhibited by T Helper Type 1 (Th1)– and Th2-inducing Cytokines}, volume={195}, ISSN={0022-1007}, url={http://dx.doi.org/10.1084/jem.20011629}, DOI={10.1084/jem.20011629}, number={5}, journal={The Journal of Experimental Medicine}, publisher={Rockefeller University Press}, author={Barrat, Franck J. and Cua, Daniel J. and Boonstra, André and Richards, David F. and Crain, Chad and Savelkoul, Huub F. and de Waal-Malefyt, René and Coffman, Robert L. and Hawrylowicz, Catherine M. and O’Garra, Anne}, year={2002}, month=mar, pages={603–616} }

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