TY - JOUR

T1 - Nonmalignant T cells stimulate growth of T-cell lymphoma cells in the presence of bacterial toxins

AU - Woetmann, Anders

AU - Lovato, Paola

AU - Eriksen, Karsten W

AU - Krejsgaard, Thorbjørn

AU - Labuda, Tord

AU - Zhang, Qian

AU - Mathiesen, Anne-Merethe

AU - Geisler, Carsten

AU - Svejgaard, Arne

AU - Wasik, Mariusz A

AU - Odum, Niels

N1 - Keywords: Antigen Presentation; CD4-Positive T-Lymphocytes; Cell Communication; Cell Line, Tumor; Cell Proliferation; Coculture Techniques; Enterotoxins; Gram-Positive Bacterial Infections; Histocompatibility Antigens Class II; Humans; Interleukin-2; Lymphoma, T-Cell, Cutaneous

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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.

U2 - 10.1182/blood-2006-04-017863

DO - 10.1182/blood-2006-04-017863

M3 - Journal article

C2 - 17179233

VL - 109

SP - 3325

EP - 3332

JO - Blood

JF - Blood

SN - 0006-4971

IS - 8

ER -