Nonmalignant T cells stimulate growth of T-cell lymphoma cells in the presence of bacterial toxins

A Woetmann, P Lovato, KW Eriksen, T Krejsgaard… - Blood, 2007 - ashpublications.org
A Woetmann, P Lovato, KW Eriksen, T Krejsgaard, T Labuda, Q Zhang, AM Mathiesen…
Blood, 2007ashpublications.org
Bacterial toxins including staphylococcal enterotoxins (SEs) have been implicated in the
pathogenesis of cutaneous T-cell lymphomas (CTCLs). Here, we investigate SE-mediated
interactions between nonmalignant T cells and malignant T-cell lines established from skin
and blood of CTCL patients. The malignant CTCL cells express MHC class II molecules that
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 …
Abstract
Bacterial toxins including staphylococcal enterotoxins (SEs) have been implicated in the pathogenesis of cutaneous T-cell lymphomas (CTCLs). Here, we investigate SE-mediated interactions between nonmalignant T cells and malignant T-cell lines established from skin and blood of CTCL patients. The malignant CTCL cells express MHC class II molecules that 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 nonmalignant T cells. In turn, the nonmalignant T cells enhance proliferation of the malignant cells in an SE- and MHC class II–dependent manner. Furthermore, SE and, in addition, alloantigen presentation by malignant CTCL cells to irradiated nonmalignant CD4+ T-cell lines also enhance 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 bidirectional cross talk between nonmalignant 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.
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