Reference : Prostaglandin E2 induces the expression of functional inhibitory CD94/NKG2A receptors...
Scientific journals : Article
Human health sciences : Immunology & infectious disease
Prostaglandin E2 induces the expression of functional inhibitory CD94/NKG2A receptors in human CD8+ T lymphocytes by a cAMP-dependent protein kinase A type I pathway.
Zeddou, Mustapha mailto [Université de Liège - ULiège > Département des sciences cliniques > Hématologie >]
Greimers, Roland [Centre Hospitalier Universitaire de Liège - CHU > > Anatomie pathologique >]
de Valensart, Nicolas [> > > >]
Nayjib, Btissam mailto [> > > >]
Tasken, Kjetil [> > > >]
Boniver, Jacques mailto [Centre Hospitalier Universitaire de Liège - CHU > > Anatomie pathologique >]
Moutschen, Michel mailto [Centre Hospitalier Universitaire de Liège - CHU > > Maladies infectieuses et médecine interne générale >]
Rahmouni, Souad mailto [Université de Liège - ULiège > Département des sciences cliniques > Immunopathologie - Transplantation >]
Biochemical Pharmacology
Elsevier Science
Yes (verified by ORBi)
United Kingdom
[en] Antigens, CD/biosynthesis/genetics/physiology ; Antigens, CD94 ; CD8-Positive T-Lymphocytes/metabolism ; Cyclic AMP/analogs & derivatives/pharmacology/physiology ; Cyclic AMP-Dependent Protein Kinases/physiology ; Dinoprostone/pharmacology ; Humans ; Lectins, C-Type/biosynthesis/genetics/physiology ; RNA, Messenger/analysis ; Receptors, Immunologic/biosynthesis/genetics/physiology ; Thionucleotides/pharmacology
[en] The CD94/NKG2A heterodimer is a natural killer receptor (NKR), which inhibits cell-mediated cytotoxicity upon interaction with MHC class I gene products. It is expressed by NK cells and by a small fraction of activated T cells, predominantly of CD8+ phenotype. Abnormal upregulation of the CD94/NKG2A inhibitory NKR on cytotoxic T cells (CTLs) could be responsible for a failure of immunosurveillance in cancer or HIV infection. In an attempt to identify the mechanisms leading to inhibitory NKR upregulation on T cells, we analyzed the expression of the CD94/NKG2A heterodimer on human CTLs activated with anti-CD3 mAb in the presence of PGE2 or with 8-CPT-cAMP, an analogue of cyclic AMP. As previously described, anti-CD3 mAb-mediated activation induced the expression of CD94/NKG2A on a small fraction of CD8+ T cells. Interestingly, when low concentrations of PGE2 or 8-CPT-cAMP were present during the culture, the proportion of CD8+ T cells expressing CD94/NKG2A was two- to five-fold higher. This upregulation was partially prevented by PKA inhibitors, such as KT5720 and Rp-8-Br-cAMP (type I selective). We also report that cAMP induces upregulation of NKG2A at the mRNA level. We further demonstrated that cross-linking of CD94 on CD8+ T cells expressing the CD94/NKG2A heterodimer inhibits their cytotoxic activity in a bispecific antibody redirected lysis assay. Our findings clearly demonstrate that the PGE2/cAMP/PKA type I axis is involved in the expression of CD94/NKG2A receptor on human CD8+ T lymphocytes.
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