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1


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Institute of Virology and Departments of
Pathology and
Dermatology, University of Cologne, Cologne, Germany
Cellular immunity plays a major role in controlling human papilloma
virus infection and development of cervical carcinoma. Mononuclear cell
infiltration possibly due to the action of chemokines becomes prominent
in the tumor tissue. In fact, the macrophage chemoattractant protein-1,
MCP-1, was detected in cervical squamous cell carcinoma in situ,
whereas absent in cultured cells. From this, unknown environmental
factors were postulated regulating chemokine expression in vivo. In
this study, we show high CD40 expression on cervical carcinoma cells
and CD40 ligand (CD40L) staining on attracted T cells in tumor tissue,
suggesting a paracrine stimulation mechanism via CD40L-CD40
interactions. We therefore investigated chemokine synthesis in
nonmalignant and malignant human papilloma virus-positive cell lines
after CD40L exposure. Constitutive expression of MCP-1, MCP-3, RANTES,
and IFN-
-inducible protein-10 was almost undetectable in all cell
lines tested. CD40L was able to induce MCP-1 production; however,
despite much higher CD40 expression in malignant cells, MCP-1 induction
was significantly lower compared with nontumorigenic cells. After
sensitization with IFN-
, another T cell-derived cytokine showing
minimal effects on CD40 expression levels, CD40 ligation led to a more
than 20-fold MCP-1 induction in carcinoma cell lines. An even stronger
effect was observed for IFN-
-inducible protein-10. Our study
highlights the synergism of T cell-derived mediators such as CD40L and
IFN-
for chemokine responses in cervical carcinoma cells, helping to
understand the chemokine expression patterns observed in
vivo.
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