International Immunology, Vol. 15, No. 12, pp. 1495-1504,
December 2003
© 2003 Japanese Society for Immunology
Transforming growth factor-ß inhibits human antigen-specific CD4+ T cell proliferation without modulating the cytokine response
1 Department of Dermatology/Allergology, University Medical Center, PO Box 85.500, 3508 GA Utrecht, The Netherlands 2 Swiss Institute of Allergy and Asthma Research (SIAF), CH-7270 Davos, Switzerland 3 Numico Research, PO Box 7005, 6700 CA Wageningen, The Netherlands
Correspondence to: M. Tiemessen; E-mail: m.tiemessen{at}azu.nl
Transmitting editor: S. L. Swain
Transforming growth factor (TGF)-ß has been demonstrated to play a key role in the regulation of the immune response, mainly by its suppressive function towards cells of the immune system. In humans, the effect of TGF-ß on antigen-specific established memory T cells has not been investigated yet. In this study antigen-specific CD4+ T cell clones (TCC) were used to determine the effect of TGF-ß on antigen-specific proliferation, the activation status of the T cells and their cytokine production. This study demonstrates that TGF-ß is an adequate suppressor of antigen-specific T cell proliferation, by reducing the cell-cycle rate rather than induction of apoptosis. Addition of TGF-ß resulted in increased CD69 expression and decreased CD25 expression on T cells, indicating that TGF-ß is able to modulate the activation status of in vivo differentiated T cells. On the contrary, the antigen-specific cytokine production was not affected by TGF-ß. Although TGF-ß was suppressive towards the majority of the T cells, insensitivity of a few TCC towards TGF-ß was also observed. This could not be correlated to differential expression of TGF-ß signaling molecules such as Smad3, Smad7, SARA (Smad anchor for receptor activation) and Hgs (hepatocyte growth factor-regulated tyrosine kinase substrate). In summary, TGF-ß has a pronounced inhibitory effect on antigen-specific T cell proliferation without modulating their cytokine production.
Keywords: CD25, IL-10, immunosuppression, Smad protein, tolerance
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Gereke, S. Jung, J. Buer, and D. Bruder Alveolar Type II Epithelial Cells Present Antigen to CD4+ T Cells and Induce Foxp3+ Regulatory T Cells Am. J. Respir. Crit. Care Med., March 1, 2009; 179(5): 344 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Das and A. D. Levine TGF-{beta} Inhibits IL-2 Production and Promotes Cell Cycle Arrest in TCR-Activated Effector/Memory T Cells in the Presence of Sustained TCR Signal Transduction J. Immunol., February 1, 2008; 180(3): 1490 - 1498. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Classen, T. Zander, D. Eggle, J. M. Chemnitz, B. Brors, I. Buchmann, A. Popov, M. Beyer, R. Eils, S. Debey, et al. Human Resting CD4+ T Cells Are Constitutively Inhibited by TGFbeta under Steady-State Conditions J. Immunol., June 1, 2007; 178(11): 6931 - 6940. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Tzachanis, L. Li, E. M. Lafuente, A. Berezovskaya, G. J. Freeman, and V. A. Boussiotis Twisted gastrulation (Tsg) is regulated by Tob and enhances TGF-{beta} signaling in activated T lymphocytes Blood, April 1, 2007; 109(7): 2944 - 2952. [Abstract] [Full Text] [PDF]
|
|