Nonmalignant T cells stimulate growth of T-cell lymphoma cells in the presence of bacterial toxins.
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.
Woetmann
Anders
A
Institute of Molecular Biology, University of Copenhagen, Blegdamsvej 3c, DK 2200 Copenhagen N, Denmark.
Lovato
Paola
P
Eriksen
Karsten W
KW
Krejsgaard
Thorbjørn
T
Labuda
Tord
T
Zhang
Qian
Q
Mathiesen
Anne-Merethe
AM
Geisler
Carsten
C
Svejgaard
Arne
A
Wasik
Mariusz A
MA
Ødum
Niels
N
D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D004768:Enterotoxins / Q000276:immunology* / Q000494:pharmacology; D016908:Gram-Positive Bacterial Infections / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D000949:Histocompatibility Antigens Class II; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology; D016410:Lymphoma, T-Cell, Cutaneous / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology
D004768:Enterotoxins; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; C026066:enterotoxin A, Staphylococcal