Submitted April 18, 2006
Accepted December 5, 2006
Non-malignant T cells stimulate growth of T-cell lymphoma
cells in the presence of bacterial toxins
Anders Woetmann, Paola Lovato, Karsten W Eriksen, Thorbjorn Krejsgaard, Tord Labuda, Qian Zhang, Anne-Merethe Mathiesen, Carsten Geisler, Arne Svejgaard, Mariusz A Wasik, and Niels Odum*
IMB, University of Copenhagen, Copenhagen, Denmark
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States
IMMI, University of Copenhagen, Copenhagen, Denmark
Department of Clinical Immunology, University Hospital of Copenhagen (Rigshospitalet), Copenhagen, Denmark
* Corresponding author; email: n.odum{at}immi.ku.dk.
Bacterial toxins including staphylococcal enterotoxins (SE) have been implicated in the pathogenesis of cutaneous T cell lymphomas (CTCL). Here, we investigate SE-mediated interactions between non-malignant T cells and malignant T-cell lines established from skin and blood of CTCL patients. The malignant CTCL cells express MHC class II molecules which are high- affinity receptors for SE. Although treatment with SE has no direct effect on the growth of the malignant CTCL cells, the SE- treated CTCL cells induce vigorous proliferation of the SE-responsive non-malignant T cells. In turn, the non-malignant T cells enhance proliferation of the malignant cells in the SE- and MHC II-dependant manner. Furthermore, SE- and, in addition, alloantigen- presentation by malignant CTCL cells to irradiated non-malignant CD4+ T cell lines also enhances proliferation of the malignant cells. The growth-promoting effect depends on direct cell-cell contact and soluble factors such as interleukin-2. In conclusion, we demonstrate that SE triggers a bi-directional cross-talk between non-malignant T cells and malignant CTCL cells that promotes growth of the malignant cells. This represents a novel mechanism by which infections with SE- producing bacteria may
contribute to pathogenesis of CTCL.
