CD28 engagement inhibits CD73-mediated regulatory activity of CD8+ T cells.
Commun Biol
; 4(1): 595, 2021 05 19.
Article
in En
| MEDLINE
| ID: mdl-34011962
ABSTRACT
CD28 is required for T cell activation as well as the generation of CD4+Foxp3+ Treg. It is unclear, however, how CD28 costimulation affects the development of CD8+ T cell suppressive function. Here, by use of Hepa1.6.gp33 in vitro killing assay and B16.gp33 tumor mouse model we demonstrate that CD28 engagement during TCR ligation prevents CD8+ T cells from becoming suppressive. Interestingly, our results showed that ectonucleotidase CD73 expression on CD8+ T cells is upregulated in the absence of CD28 costimulation. In both murine and human tumor-bearing hosts, CD73 is upregulated on CD28-CD8+ T cells that infiltrate the solid tumor. UPLC-MS/MS analysis revealed that CD8+ T cells activation without CD28 costimulation produces elevated levels of adenosine and that CD73 mediates its production. Adenosine receptor antagonists block CD73-mediated suppression. Our data support the notion that CD28 costimulation inhibits CD73 upregulation and thereby prevents CD8+ T cells from becoming suppressive. This study uncovers a previously unidentified role for CD28 costimulation in CD8+ T cell activation and suggests that the CD28 costimulatory pathway can be a potential target for cancer immunotherapy.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Melanoma, Experimental
/
Lymphocyte Activation
/
5'-Nucleotidase
/
CD28 Antigens
/
CD8-Positive T-Lymphocytes
Limits:
Animals
Language:
En
Journal:
Commun Biol
Year:
2021
Type:
Article
Affiliation country:
Taiwan