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Endothelial cells expressing an inflammatory phenotype are lysed by superantigen-targeted cytotoxic T cells

Riesbeck, Kristian LU orcid ; Billström, Anita LU ; Tordsson, Jesper LU ; Brodin, Thomas ; Kristensson, Karin and Dohlsten, Mikael (1998) In Clinical and Diagnostic Laboratory Immunology 5(5). p.675-682
Abstract

The objective of this study was to investigate whether the superantigen staphylococcal enterotoxin A (SEA), which binds to HLA class II and T-cell receptor Vβ chains, can direct cytotoxic T cells to lyse cytokine-stimulated endothelial cells (EC). In addition, we wanted to determine whether SEA- primed cytotoxic T cells could be targeted to EC surface molecules as a means of a novel cancer immunotherapy. Human umbilical vein EC (HUVEC), dermal microvascular EC (HMVEC), or the EC line EA.hy926 stimulated with gamma interferon (IFN-γ) or tumor necrosis factor alpha (TNF-α) displayed upregulated HLA class II and adhesion molecule (CD54 and CD106) expression, respectively. SEA-primed T cells induced a strong cytotoxicity against IFN- γ,-... (More)

The objective of this study was to investigate whether the superantigen staphylococcal enterotoxin A (SEA), which binds to HLA class II and T-cell receptor Vβ chains, can direct cytotoxic T cells to lyse cytokine-stimulated endothelial cells (EC). In addition, we wanted to determine whether SEA- primed cytotoxic T cells could be targeted to EC surface molecules as a means of a novel cancer immunotherapy. Human umbilical vein EC (HUVEC), dermal microvascular EC (HMVEC), or the EC line EA.hy926 stimulated with gamma interferon (IFN-γ) or tumor necrosis factor alpha (TNF-α) displayed upregulated HLA class II and adhesion molecule (CD54 and CD106) expression, respectively. SEA-primed T cells induced a strong cytotoxicity against IFN- γ,- and TNF-α-activated EA.hy926 which had been preincubated with SEA. Blocking of CD54 completely abrogated the T-cell attack. SEA-D227A, which has a mutated class II binding site, did not promote any cytotoxicity. A strong lysis was observed when a fusion protein consisting of protein A and SEA- D227A was added together with T cells to TNF-α-induced EA.hy926 and HUVEC precoated with monoclonal antibodies (MAb) directed against HLA class I, CD54, or CD106 molecules. Finally, an scFv antibody fragment reactive with an unknown EC antigen was fused with SEA-D227A. Both EA.hy926 and HMVEC were efficiently lysed by scFv-SEA-D227A-triggered cytotoxic T cells. Taken together, superantigen-activated T-cell-dependent EC killing was induced when EC expressed an inflammatory phenotype. Moreover, specific MAb targeting of the superantigen to surface antigens induced EC lysis. Our data suggest that directed T-cell-mediated lysis of unwanted proliferating EC, such as those in the tumor microvasculature, can be clinically useful.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Clinical and Diagnostic Laboratory Immunology
volume
5
issue
5
pages
675 - 682
publisher
American Society for Microbiology
external identifiers
  • scopus:0032437060
  • pmid:9729535
ISSN
1071-412X
language
English
LU publication?
yes
id
513c3e00-8658-4ab6-a463-16cbe869bdcc
date added to LUP
2019-06-07 15:22:51
date last changed
2024-01-01 09:35:20
@article{513c3e00-8658-4ab6-a463-16cbe869bdcc,
  abstract     = {{<p>The objective of this study was to investigate whether the superantigen staphylococcal enterotoxin A (SEA), which binds to HLA class II and T-cell receptor Vβ chains, can direct cytotoxic T cells to lyse cytokine-stimulated endothelial cells (EC). In addition, we wanted to determine whether SEA- primed cytotoxic T cells could be targeted to EC surface molecules as a means of a novel cancer immunotherapy. Human umbilical vein EC (HUVEC), dermal microvascular EC (HMVEC), or the EC line EA.hy926 stimulated with gamma interferon (IFN-γ) or tumor necrosis factor alpha (TNF-α) displayed upregulated HLA class II and adhesion molecule (CD54 and CD106) expression, respectively. SEA-primed T cells induced a strong cytotoxicity against IFN- γ,- and TNF-α-activated EA.hy926 which had been preincubated with SEA. Blocking of CD54 completely abrogated the T-cell attack. SEA-D227A, which has a mutated class II binding site, did not promote any cytotoxicity. A strong lysis was observed when a fusion protein consisting of protein A and SEA- D227A was added together with T cells to TNF-α-induced EA.hy926 and HUVEC precoated with monoclonal antibodies (MAb) directed against HLA class I, CD54, or CD106 molecules. Finally, an scFv antibody fragment reactive with an unknown EC antigen was fused with SEA-D227A. Both EA.hy926 and HMVEC were efficiently lysed by scFv-SEA-D227A-triggered cytotoxic T cells. Taken together, superantigen-activated T-cell-dependent EC killing was induced when EC expressed an inflammatory phenotype. Moreover, specific MAb targeting of the superantigen to surface antigens induced EC lysis. Our data suggest that directed T-cell-mediated lysis of unwanted proliferating EC, such as those in the tumor microvasculature, can be clinically useful.</p>}},
  author       = {{Riesbeck, Kristian and Billström, Anita and Tordsson, Jesper and Brodin, Thomas and Kristensson, Karin and Dohlsten, Mikael}},
  issn         = {{1071-412X}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{5}},
  pages        = {{675--682}},
  publisher    = {{American Society for Microbiology}},
  series       = {{Clinical and Diagnostic Laboratory Immunology}},
  title        = {{Endothelial cells expressing an inflammatory phenotype are lysed by superantigen-targeted cytotoxic T cells}},
  volume       = {{5}},
  year         = {{1998}},
}