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
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