CD28 engagement inhibits CD73-mediated regulatory activity of CD8+ T cells
| Autor: | Pei Wen Hsiao, Lu Cheng Kuo, Hong Nerng Ho, Betty A. Wu-Hsieh, Hung-Ju Lin, Chih Yu Lin, Huan Tsung Chang, Yi-Ting Chen, Jean Lu, Been Ren Lin, Hsiang Yu Chang, Yo-Ping Lai, Hsiao Chin Chen, Patrick Chow-In Ko, John T. Kung, Shu-Ching Chen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Chemistry QH301-705.5 medicine.medical_treatment T cell T-cell receptor Medicine (miscellaneous) CD28 FOXP3 chemical and pharmacologic phenomena hemic and immune systems General Biochemistry Genetics and Molecular Biology Cell biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Cancer immunotherapy medicine Cytotoxic T cell Biology (General) General Agricultural and Biological Sciences Cell activation CD8 030215 immunology |
| Zdroj: | Communications Biology, Vol 4, Iss 1, Pp 1-12 (2021) |
| ISSN: | 2399-3642 |
| Popis: | 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. Lai et al. report that the immunosuppressive molecule CD73 is negatively regulated by CD28 costimulation during CD8+ T cell activation. Their study implicates a lack of CD28 costimulation renders CD8+ T cells immunosuppressive and less able to eliminate solid tumors. |
| Databáze: | OpenAIRE |
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