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rdf:type |
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lifeskim:mentions |
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pubmed:dateCreated |
2002-11-19
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pubmed:abstractText |
IFN-gamma regulates the immunogenicity of target cells by increasing their expression of HLA class I molecules. This facilitates the T cell receptor-mediated recognition by CD8(+) T cells but decreases target cell sensitivity to lysis by NK cells due to engagement of inhibitory NK receptors. In this study, short-term tumor cell lines from patients with advanced ovarian carcinomas were established. We demonstrate the paradoxical finding that IFN-gamma treatment of these short-term ovarian carcinoma cell lines (OVACs) resulted in resistance of tumor cells to lysis by peptide- and allospecific CD8(+) T cells. Blocking experiments revealed that this phenomenon was dependent on enhanced inhibitory signalling via CD94/NKG2A receptors expressed on the effector cells. This was associated with increased expression of HLA-E mRNA and HLA-G at the protein level in IFN-gamma-treated OVACs. Furthermore, pulsing of untreated OVACs with the leader sequence peptide of HLA-G protected these cells from lysis by CTLs, thus mimicking the inhibitory effect of IFN-gamma. This study provides evidence that CD94/NKG2A receptors play an important role in regulating T cell activity against tumors and shows that IFN-gamma modulation of target cells may shift the balance of triggering and inhibitory signals to T cells, turning off their cytolytic activity.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/12438449-10213506,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12438449-10225437,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12438449-10358773,
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pubmed:language |
eng
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/HLA Antigens,
http://linkedlifedata.com/resource/pubmed/chemical/HLA-A Antigens,
http://linkedlifedata.com/resource/pubmed/chemical/HLA-A11 Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/HLA-A2 Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/HLA-G Antigens,
http://linkedlifedata.com/resource/pubmed/chemical/Histocompatibility Antigens Class I,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/KLRC1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/KLRD1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Lectins, C-Type,
http://linkedlifedata.com/resource/pubmed/chemical/NK Cell Lectin-Like Receptor...,
http://linkedlifedata.com/resource/pubmed/chemical/NK Cell Lectin-Like Receptor...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Sorting Signals,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Natural Killer Cell,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
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pubmed:status |
MEDLINE
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pubmed:author |
pubmed-author:CarlstenMattiasM,
pubmed-author:KiesslingRolfR,
pubmed-author:LevitskayaJelenaJ,
pubmed-author:LevitskyVictorV,
pubmed-author:MalmbergKarl-JohanKJ,
pubmed-author:MorettaAlessandroA,
pubmed-author:NorellHåkanH,
pubmed-author:RabbaniHodjattallahH,
pubmed-author:SöderströmKalleK,
pubmed-author:SchedvinsKjellK,
pubmed-author:de MatosCristina TeixeiraCT
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1515-23
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pubmed:dateRevised |
2011-11-17
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pubmed:articleTitle |
IFN-gamma protects short-term ovarian carcinoma cell lines from CTL lysis via a CD94/NKG2A-dependent mechanism.
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pubmed:affiliation |
Immune and Gene Therapy Laboratory, Cancer Center Karolinska, Department of Oncology and Pathology, Stockholm, Sweden.
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