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CD70 expression determines the therapeutic efficacy of expanded human regulatory T cells.
- Source :
- Communications Biology; 7/14/2020, Vol. 3 Issue 1, p1-17, 17p
- Publication Year :
- 2020
-
Abstract
- 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<superscript>−</superscript>CD70<superscript>+</superscript> 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. Regulatory T cells maintain immune homeostasis and help control development of autoimmunity and allergy. Arroyo-Hornero et al show that upon prolonged stimulation, regulatory T cells may switch to an immunostimulatory phenotype by upregulating the expression of the co-stimulatory molecule CD70. [ABSTRACT FROM AUTHOR]
- Subjects :
- TREATMENT effectiveness
T cells
HOMEOSTASIS
IMMUNOLOGICAL adjuvants
RNA sequencing
Subjects
Details
- Language :
- English
- ISSN :
- 23993642
- Volume :
- 3
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Communications Biology
- Publication Type :
- Academic Journal
- Accession number :
- 144564672
- Full Text :
- https://doi.org/10.1038/s42003-020-1097-8