Experiment Overview
| Repository ID: | FR-FCM-Z3GZ | Experiment name: | Fanelli et al. Mass cytometry data | MIFlowCyt score: | 64.82% |
| Primary researcher: | Marco Romano | PI/manager: | Marco Romano | Uploaded by: | Marco Romano |
| Experiment dates: | 2019-02-13 - 2021-03-19 | Dataset uploaded: | Feb 2021 | Last updated: | Mar 2021 |
| Keywords: | [PD/PD-L1] [mass cytometry] [Tregs] | Manuscripts: | |||
| Organizations: |
King's College London, King's College London, London, London (United Kingdom)
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| Purpose: | Effect of PD-L1 engagment on CD4 cells | ||||
| Conclusion: | Programmed death cell receptor 1 (PD-1) is expressed on T cells upon T cell receptor (TCR) stimulation. High levels of expression are found on T cells during chronic infection, on tumour-infiltrating T cells and memory T cells. PD-1 ligand 1 (PD-L1) is expressed in most tumour environments, and its binding to PD-1 on T cells drives them either to apoptosis or conversion into regulatory T cells (Tregs). However, the fact that PD-L1 itself is also expressed on T cells upon activation has been largely neglected. In this study, we demonstrated that cross-linking of PD-L1 on human CD25-depleted CD4+ T cells, in combination with signalling through CD3/TCR induces their conversion into highly suppressive T cells. Furthermore, this effect was most prominent in memory T cells. PD-L1 co-stimulation on T cells resulted in reduced levels of ERK phosphorylation and decreased mTOR signalling. Importantly, T cells from rheumatoid arthritis patients exhibited high basal levels of phosphorylated ERK and following PD-L1 cross-linking ERK signalling failed to be down modulated, making them resistant to Treg conversion. Altogether our results suggest that engagement of PD-L1 on memory T cells could play an important role in resolving inflammatory responses and its failure could contribute to ongoing autoimmunity. | ||||
| Comments: | FCS files of manually gated live cells following normalization | ||||
| Funding: | British Heart Foundation | ||||
| Quality control: | CD and intracellular antigen analysis | ||||
Experiment variables
| Conditions | |
|---|---|
| · AntiCD3 | D1 AntiCD3_normalized_CD4+.fcs · D2 AntiCD3_normalized_CD4+.fcs · D3 AntiCD3_normalized_CD4+.fcs |
| · AntiCD3_CD28 | D1 AntiCD3-28_normalized_CD4+.fcs · D2 AntiCD3-28_normalized_CD4+.fcs · D3 AntiCD3-28_normalized_CD4+.fcs |
| · AntiCD3_PD-L1 | D1 AntiCD3-PDL1 _normalized_CD4+.fcs · D2 AntiCD3-PDL1_normalized_CD4+.fcs · D3 AntiCD3-PDL1_normalized_CD4+.fcs |
| Individuals | |
|---|---|
| · D1 | D1 AntiCD3-28_normalized_CD4+.fcs · D1 AntiCD3-PDL1 _normalized_CD4+.fcs · D1 AntiCD3_normalized_CD4+.fcs |
| · D2 | D2 AntiCD3-28_normalized_CD4+.fcs · D2 AntiCD3-PDL1_normalized_CD4+.fcs · D2 AntiCD3_normalized_CD4+.fcs |
| · D3 | D3 AntiCD3-28_normalized_CD4+.fcs · D3 AntiCD3-PDL1_normalized_CD4+.fcs · D3 AntiCD3_normalized_CD4+.fcs |
