International Immunology Advance Access originally published online on July 12, 2004
International Immunology 2004 16(9):1241-1249; doi:10.1093/intimm/dxh126
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© 2004 The Japanese Society for Immunology
TGFß regulates the CD4+CD25+ T-cell pool and the expression of Foxp3 in vivo
1 Department of Medicine, 2 Institute of Pathology and 3 Institute of Immunology, Faculty of Medicine, Johannes Gutenberg-University, Mainz, Germany
4 Faculty of Veterinary Medicine, Center for Biotechnology and Biomedicine, University of Leipzig, Leipzig, Germany
Correspondence to: C. Schramm; E-mail: schramm{at}uni-mainz.de
Factors influencing the development of CD4+CD25+ T-cells in vivo are poorly understood. In order to investigate the contribution of TGFß1 to the development and function of CD4+CD25+ T-cells, we generated a gain of function mutation resulting in the overexpression of an active form of TGFß1 in T-cells under control of the human CD2 promoter. In peripheral lymphoid organs and in the thymus, the frequency of CD4+CD25+ T-cells was increased in transgenic mice. This appeared to be due to an autocrine effect of TGFß on T-cells, since concomitant impairment of TGFß-signaling in double transgenic mice resulted in a phenotype similar to wild type. In contrast, in single transgenic mice with impaired TGFß-signaling in T-cells, CD4+CD25+ T-cell numbers were reduced in peripheral lymphoid organs but not in the thymus. In addition, TGFß was found to regulate the expression of Foxp3 in vivo, a transcription factor essential for the generation and function of regulatory T-cells. In CD4+CD25+ T-cells, TGFß1 increased the expression of Foxp3, whereas a decreased expression was seen in CD4+CD25+ T-cells with impaired TGFß-signaling. TGFß1 induced the expression of IL-10 in transgenic T-cells, but the increased in vitro suppressive capacity observed in transgenic CD4+CD25+ T-cells was due to the secretion of TGFß and not IL-10. Therefore, our study provides in vivo evidence for a role of TGFß in the homeostasis of CD4+CD25+ T-cells.
Keywords: IL-10, regulatory T-cells, TGFß-signalling, thymus, tolerance
The first two authors have contributed equally to this work.
Transmitting editor: A. Radbruch
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