Autocrine stimulation of rhadinovirus-transformed T cells by the chemokine CCL1/I-309.
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-gamma and tumor necrosis factor-alpha 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.
Tamgüney
Gültekin
G
Virology Department, Ruprecht Karls University Heidelberg, Im Neuenheimer Feld 324, D-69120 Heidelberg, Germany.
Van Snick
Jacques
J
Fickenscher
Helmut
H
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D054402:Chemokine CCL1; D019742:Chemokines, CC / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D016399:Lymphoma, T-Cell / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D054401:Receptors, CCR8; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D018144:Rhadinovirus / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism* / Q000821:virology
D018931:Antineoplastic Agents, Hormonal; C065971:CCL1 protein, human; C103330:CCR8 protein, human; C502258:Ccl1 protein, mouse; D054402:Chemokine CCL1; D019742:Chemokines, CC; D054401:Receptors, CCR8; D019707:Receptors, Chemokine; D003907:Dexamethasone