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

Anders Woetmann; Paola Lovato; Karsten W Eriksen; Thorbjørn Krejsgaard; Tord Labuda; Qian Zhang; Anne-Merethe Mathiesen; Carsten Geisler; Arne Svejgaard; Mariusz A Wasik; Niels Odum

doi:10.1182/blood-2006-04-017863

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

Anders Woetmann, Paola Lovato, Karsten W Eriksen, Thorbjørn Krejsgaard, Tord Labuda, Qian Zhang, Anne-Merethe Mathiesen, Carsten Geisler, Arne Svejgaard, Mariusz A Wasik, Niels Odum

51 Citations (Scopus)

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.

Original language	English
Journal	Blood
Volume	109
Issue number	8
Pages (from-to)	3325-32
Number of pages	7
ISSN	0006-4971
DOIs	https://doi.org/10.1182/blood-2006-04-017863
Publication status	Published - 2007

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@article{78c22160b09f11ddb538000ea68e967b,

title = "Nonmalignant T cells stimulate growth of T-cell lymphoma cells in the presence of bacterial toxins",

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.",

author = "Anders Woetmann and Paola Lovato and Eriksen, {Karsten W} and Thorbj{\o}rn Krejsgaard and Tord Labuda and Qian Zhang and Anne-Merethe Mathiesen and Carsten Geisler and Arne Svejgaard and Wasik, {Mariusz A} and Niels Odum",

note = "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",

year = "2007",

doi = "10.1182/blood-2006-04-017863",

language = "English",

volume = "109",

pages = "3325--32",

journal = "Blood",

issn = "0006-4971",

publisher = "American Society of Hematology",

number = "8",

}

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

SN - 0006-4971

VL - 109

SP - 3325

EP - 3332

JO - Blood

JF - Blood

IS - 8

ER -

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

Abstract

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