CD70 expression determines the therapeutic efficacy of expanded human regulatory T cells
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 significa...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Springer Nature
2020
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| _version_ | 1797096769102807040 |
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| author | Arroyo Hornero, R Georgiadis, C Hua, P Trzupek, D He, L-Z Qasim, W Todd, JA Ferreira, RC Wood, KJ Issa, F Hester, J |
| author_facet | Arroyo Hornero, R Georgiadis, C Hua, P Trzupek, D He, L-Z Qasim, W Todd, JA Ferreira, RC Wood, KJ Issa, F Hester, J |
| author_sort | Arroyo Hornero, R |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T04:46:15Z |
| format | Journal article |
| id | oxford-uuid:d3642f13-06da-4278-84f0-bd1601342fbf |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:46:15Z |
| publishDate | 2020 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:d3642f13-06da-4278-84f0-bd1601342fbf2022-03-27T08:10:56ZCD70 expression determines the therapeutic efficacy of expanded human regulatory T cellsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d3642f13-06da-4278-84f0-bd1601342fbfEnglishSymplectic ElementsSpringer Nature2020Arroyo Hornero, RGeorgiadis, CHua, PTrzupek, DHe, L-ZQasim, WTodd, JAFerreira, RCWood, KJIssa, FHester, JRegulatory 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. |
| spellingShingle | Arroyo Hornero, R Georgiadis, C Hua, P Trzupek, D He, L-Z Qasim, W Todd, JA Ferreira, RC Wood, KJ Issa, F Hester, J CD70 expression determines the therapeutic efficacy of expanded human regulatory T cells |
| title | CD70 expression determines the therapeutic efficacy of expanded human regulatory T cells |
| title_full | CD70 expression determines the therapeutic efficacy of expanded human regulatory T cells |
| title_fullStr | CD70 expression determines the therapeutic efficacy of expanded human regulatory T cells |
| title_full_unstemmed | CD70 expression determines the therapeutic efficacy of expanded human regulatory T cells |
| title_short | CD70 expression determines the therapeutic efficacy of expanded human regulatory T cells |
| title_sort | cd70 expression determines the therapeutic efficacy of expanded human regulatory t cells |
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