International Immunology Advance Access published online on July 12, 2004
International Immunology, doi:10.1093/intimm/dxh126
© 2004 by The Japanese Society for Immunology
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1 Department of Medicine, Johannes Gutenberg-University, Mainz, Germany
* To whom correspondence should be addressed. 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 TGF The first two authors have contributed equally to this work.
Accepted June 14, 2004
Article
TGF
regulates the CD4+CD25+ T-cell pool and the expression of Foxp3 in vivo
2 Institute of Pathology, Johannes Gutenberg-University, Mainz, Germany
3 Institute of Immunology, Faculty of Medicine, Johannes Gutenberg-University, Mainz, Germany
4 Department of Medicine, Johannes Gutenberg-University, Mainz, Germany; Faculty of Veterinary Medicine, Center for Biotechnology and Biomedicine, University of Leipzig, Leipzig, Germany
Abstract 
1 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 TGF1 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 TGF on T-cells, since concomitant impairment of TGF-signaling in double transgenic mice resulted in a phenotype similar to wild type. In contrast, in single transgenic mice with impaired TGF-signaling in T-cells, CD4+CD25+ T-cell numbers were reduced in peripheral lymphoid organs but not in the thymus. In addition, TGF 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, TGF1 increased the expression of Foxp3, whereas a decreased expression was seen in CD4+CD25+ T-cells with impaired TGF-signaling. TGF1 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 TGF and not IL-10. Therefore, our study provides in vivo evidence for a role of TGF in the homeostasis of CD4+CD25+ T-cells.-signalling; thymus; tolerance.
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