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Autocrine stimulation of rhadinovirus-transformed T cells by the chemokine CCL1/I-309

Oncogene volume 23, pages 8475–8485 (2004)Cite this article

Abstract

The rhadinovirus herpesvirus saimiri transforms human T lymphocytes to stable growth in culture. Besides the viral oncogenes stpC and tip, little is understood about the transformation process at the cellular level. To identify cellular factors that might contribute to growth transformation, we compared cellular gene expression in pairs of herpesvirus saimiri-transformed and nontransformed human T-cell clones. Using cDNA arrays and suppressive subtractive hybridization, we were able to identify the chemokine CCL1/I-309 as one of the few cellular genes that are strongly overexpressed in T cells after growth transformation with herpesvirus saimiri. The transformed T cells expressed CCR8, the receptor for CCL1, which rapidly induced intracellular calcium ion levels. Neutralizing antibodies to CCL1 led to reduced secretion of interferon-γ and tumor necrosis factor-α as well as to reduced proliferation rates in transformed T cells. Thus, we propose that growth transformation of human T cells with herpesvirus saimiri gives rise to an autocrine loop where the proliferation of transformed T cells is supported by the endogenous production of the chemokine CCL1.

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Acknowledgements

We thank Jean-Christophe Renauld and Tobias Ruckes for helpful suggestions and Heide Pirzer for critically reading the manuscript. Gültekin Tamgüney was supported by a graduate student fellowship of the Boehringer Ingelheim Fonds. The project was funded by the Wilhelm Sander-Stiftung and by the Deutsche Forschungsgemeinschaft.

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Authors and Affiliations

  1. Virology Department, Ruprecht Karls University Heidelberg, Im Neuenheimer Feld 324, Heidelberg, D-69120, Germany

    Gültekin Tamgüney & Helmut Fickenscher

  2. Institute for Neurodegenerative Diseases, University of California San Francisco, 513 Parnassus Avenue, 94143-0518, CA, USA

    Gültekin Tamgüney

  3. Ludwig Institute for Cancer Research and Experimental Medicine Unit, Université Catholique de Louvain, Avenue Hippocrate 74, Brussels, B-1200, Belgium

    Jacques Van Snick

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  1. Gültekin Tamgüney
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Correspondence to Helmut Fickenscher.

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Tamgüney, G., Van Snick, J. & Fickenscher, H. Autocrine stimulation of rhadinovirus-transformed T cells by the chemokine CCL1/I-309. Oncogene 23, 8475–8485 (2004). https://doi.org/10.1038/sj.onc.1207903

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