T-cell clones from Th1, Th17 or Th1/17 lineages and their signature cytokines have different capacity to activate endothelial cells or synoviocytes.
To compare the direct effect of cytokines on synoviocytes and endothelial cells to the effects of supernatants from Th1, Th17 and Th1/17 clones and the direct cell-cell interactions with the same clones.



Th17 and Th1/17 clones were obtained from the CD161+CCR6+ fraction and Th1 clones from the CD161-CCR6- fraction of human CD4+ T-cells. Endothelial cells or synoviocytes were cultured in the presence of either isolated pro-inflammatory cytokines (IL-17 and/or TNF-α) or supernatants from the T-cell clones or co-cultured with T-cell clones themselves. IL-6 and IL-8 expression and production were analyzed.



IL-17 and TNF-α induced IL-6 and IL-8 expression, although IL-17 alone had a limited effect on endothelial cells compared to synoviocytes. Supernatants from activated T-helper clones also induced IL-6 and IL-8 expression but with discrepancies between endothelial cells and synoviocytes. Endothelial cells were mostly activated by Th1 clone supernatants whereas synoviocytes were activated by all T-cell subtypes. Finally, cell-cell contact experiments showed a great heterogeneity among cell clones, even from the same lineage. IL-6 expression was mostly induced by contact with Th1 clones both in endothelial and mesenchymal cells whereas IL-8 expression was induced by all T-cell clones whatever their phenotype.



We showed that endothelial cells were much more sensitive to Th1 activation whereas synoviocytes were activated by all T-helper lineages. This work highlights the heterogeneity of interactions between T-cells and stromal cells through soluble factors or direct cell contact.
Department of Immunology and Rheumatology, Immunogenomics and Inflammation Research Unit EA 4130, University of Lyon, Edouard Herriot Hospital, Lyon, France. Electronic address: fabien.lavocat@chu-lyon.fr.
Fabien
F
Lavocat
Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy. Electronic address: laura.maggi@unifi.it.
Laura
L
Maggi
Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy. Electronic address: francesco.annunziato@unifi.it.
Francesco
F
Annunziato
Department of Immunology and Rheumatology, Immunogenomics and Inflammation Research Unit EA 4130, University of Lyon, Edouard Herriot Hospital, Lyon, France. Electronic address: pierre.miossec@univ-lyon1.fr.
Pierre
P
Miossec
D016207:Cytokines / Q000276:immunology*; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000276:immunology*; D006801:Humans; D008297:Male; D000070918:Synoviocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
D016207:Cytokines
Endothelial cell; Fibroblast; Inflammation; Synoviocyte; T-helper cell