CD70 expression determines the therapeutic efficacy of expanded human regulatory T cells.
Rebeca Arroyo HorneroChristos GeorgiadisPeng HuaDominik TrzupekLi-Zhen HeWaseem QasimJohn A ToddRicardo C FerreiraKathryn J WoodFadi IssaJoanna HesterPublished in: Communications biology (2020)
Regulatory T cells (Tregs) are critical mediators of immune homeostasis. The co-stimulatory molecule CD27 is a marker of highly suppressive Tregs, although the role of the CD27-CD70 receptor-ligand interaction in Tregs is not clear. Here we show that after prolonged in vitro stimulation, a significant proportion of human Tregs gain stable CD70 expression while losing CD27. The expression of CD70 in expanded Tregs is associated with a profound loss of regulatory function and an unusual ability to provide CD70-directed co-stimulation to TCR-activated conventional T cells. Genetic deletion of CD70 or its blockade prevents Tregs from delivering this co-stimulatory signal, thus maintaining their regulatory activity. High resolution targeted single-cell RNA sequencing of human peripheral blood confirms the presence of CD27-CD70+ Treg cells. These findings have important implications for Treg-based clinical studies where cells are expanded over extended periods in order to achieve sufficient treatment doses.
Keyphrases
- regulatory t cells
- endothelial cells
- single cell
- poor prognosis
- high resolution
- dendritic cells
- nk cells
- induced apoptosis
- transcription factor
- immune response
- binding protein
- cell proliferation
- autism spectrum disorder
- high throughput
- gene expression
- oxidative stress
- pluripotent stem cells
- rna seq
- signaling pathway
- long non coding rna
- liquid chromatography
- tandem mass spectrometry