TGFbeta regulates the CD4+CD25+ T-cell pool and the expression of Foxp3 in vivo
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TGFbeta regulates the CD4+CD25+ T-cell pool and the expression of Foxp3 in vivo. / Schramm, Christoph; Huber, Samuel; Protschka, Martina; Czochra, P; Burg, Jürgen; Schmitt, Edgar; Lohse, Ansgar W; Galle, Peter R; Blessing, Manfred.
In: International immunology, Vol. 16, No. 9, 09.2004, p. 1241-1249.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - TGFbeta regulates the CD4+CD25+ T-cell pool and the expression of Foxp3 in vivo
AU - Schramm, Christoph
AU - Huber, Samuel
AU - Protschka, Martina
AU - Czochra, P
AU - Burg, Jürgen
AU - Schmitt, Edgar
AU - Lohse, Ansgar W
AU - Galle, Peter R
AU - Blessing, Manfred
PY - 2004/9
Y1 - 2004/9
N2 - Factors influencing the development of CD4+CD25+ T-cells in vivo are poorly understood. In order to investigate the contribution of TGFbeta1 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 TGFbeta1 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 TGFbeta on T-cells, since concomitant impairment of TGFbeta-signaling in double transgenic mice resulted in a phenotype similar to wild type. In contrast, in single transgenic mice with impaired TGFbeta-signaling in T-cells, CD4+CD25+ T-cell numbers were reduced in peripheral lymphoid organs but not in the thymus. In addition, TGFbeta 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, TGFbeta1 increased the expression of Foxp3, whereas a decreased expression was seen in CD4+CD25+ T-cells with impaired TGFbeta-signaling. TGFbeta1 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 TGFbeta and not IL-10. Therefore, our study provides in vivo evidence for a role of TGFbeta in the homeostasis of CD4+CD25+ T-cells.
AB - Factors influencing the development of CD4+CD25+ T-cells in vivo are poorly understood. In order to investigate the contribution of TGFbeta1 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 TGFbeta1 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 TGFbeta on T-cells, since concomitant impairment of TGFbeta-signaling in double transgenic mice resulted in a phenotype similar to wild type. In contrast, in single transgenic mice with impaired TGFbeta-signaling in T-cells, CD4+CD25+ T-cell numbers were reduced in peripheral lymphoid organs but not in the thymus. In addition, TGFbeta 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, TGFbeta1 increased the expression of Foxp3, whereas a decreased expression was seen in CD4+CD25+ T-cells with impaired TGFbeta-signaling. TGFbeta1 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 TGFbeta and not IL-10. Therefore, our study provides in vivo evidence for a role of TGFbeta in the homeostasis of CD4+CD25+ T-cells.
KW - Animals
KW - CD2 Antigens/physiology
KW - CD4 Antigens/analysis
KW - DNA-Binding Proteins/analysis
KW - Forkhead Transcription Factors
KW - Interleukin-10/biosynthesis
KW - Mice
KW - Mice, Transgenic
KW - Receptors, Interleukin-2/analysis
KW - T-Lymphocyte Subsets/physiology
KW - Transforming Growth Factor beta/physiology
U2 - 10.1093/intimm/dxh126
DO - 10.1093/intimm/dxh126
M3 - SCORING: Journal article
C2 - 15249539
VL - 16
SP - 1241
EP - 1249
JO - INT IMMUNOL
JF - INT IMMUNOL
SN - 0953-8178
IS - 9
ER -