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Synergistic interactions of CD4+ and CD8+ T cell subsets with human vascular endothelial cells in primary
C J Brooks1, A Stackpoole, C O Savage
1Vascular Biology Team, Clinical Research Centre, Harrow, UK.
The ability of subcultured human vascular endothelial cells (EC) to provide immune accessory functions for proliferative responses of highly purified allogeneic CD4+ and CD8+ T cells has been examined. CD4+ T cells proliferated in response to IFN-gamma-pretreated EC which expressed class II molecules, but not to untreated EC. CD8+ T cells proliferated to MHC class I molecules expressed on both untreated and IFN-gamma-treated EC. Combined populations of CD4+ and CD8+ T cells showed synergistic, rather than additive, responses to both untreated and IFN-gamma-treated EC. Furthermore, CD8+ T cells were able to induce MHC class II expression on endothelial cells and this induction could be inhibited by an anti-IFN-gamma mAb. The synergistic response obtained by co-culturing CD4+ and CD8+ T cells with vascular EC was completely inhibited by the same anti-IFN-gamma mAb. These studies suggest that CD4+ and CD8+ T cells recognise and proliferate to allogeneic MHC molecules expressed by EC. CD4+ and CD8+ responses are synergistic under the conditions tested and this synergism appears to be due to induction of MHC class II antigens on EC by IFN-gamma secreted from CD8+ T cells.
The ability of subcultured human vascular endothelial cells (EC) to provide immune accessory functions for proliferative responses of highly purified allogeneic CD4+ and CD8+ T cells has been examined. CD4+ T cells proliferated in response to IFN-gamma-pretreated EC which expressed class II molecules, but not to untreated EC. CD8+ T cells proliferated to MHC class I molecules expressed on both untreated and IFN-gamma-treated EC. Combined populations of CD4+ and CD8+ T cells showed synergistic, rather than additive, responses to both untreated and IFN-gamma-treated EC. Furthermore, CD8+ T cells were able to induce MHC class II expression on endothelial cells and this induction could be inhibited by an anti-IFN-gamma mAb. The synergistic response obtained by co-culturing CD4+ and CD8+ T cells with vascular EC was completely inhibited by the same anti-IFN-gamma mAb. These studies suggest that CD4+ and CD8+ T cells recognise and proliferate to allogeneic MHC molecules expressed by EC. CD4+ and CD8+ responses are synergistic under the conditions tested and this synergism appears to be due to induction of MHC class II antigens on EC by IFN-gamma secreted from CD8+ T cells.