B7-H7 (HHLA2) inhibits T-cell activation and proliferation in the presence of TCR and CD28 signaling.
Checkpoint pathway
T cell inhibition
T cell transcriptomics
Journal
Cellular & molecular immunology
ISSN: 2042-0226
Titre abrégé: Cell Mol Immunol
Pays: China
ID NLM: 101242872
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
06
06
2019
accepted:
20
12
2019
revised:
20
12
2019
pubmed:
2
2
2020
medline:
27
1
2022
entrez:
2
2
2020
Statut:
ppublish
Résumé
Modulation of T-cell responses has played a key role in treating cancers and autoimmune diseases. Therefore, understanding how different receptors on T cells impact functional outcomes is crucial. The influence of B7-H7 (HHLA2) and CD28H (TMIGD2) on T-cell activation remains controversial. Here we examined global transcriptomic changes in human T cells induced by B7-H7. Stimulation through TCR with OKT3 and B7-H7 resulted in modest fold changes in the expression of select genes; however, these fold changes were significantly lower than those induced by OKT3 and B7-1 stimulation. The transcriptional changes induced by OKT3 and B7-H7 were insufficient to provide functional stimulation as measured by evaluating T-cell proliferation and cytokine production. Interestingly, B7-H7 was coinhibitory when simultaneously combined with TCR and CD28 stimulation. This inhibitory activity was comparable to that observed with PD-L1. Finally, in physiological assays using T cells and APCs, blockade of B7-H7 enhanced T-cell activation and proliferation, demonstrating that this ligand acts as a break signal. Our work defines that the transcriptomic changes induced by B7-H7 are insufficient to support full costimulation with TCR signaling and, instead, B7-H7 inhibits T-cell activation and proliferation in the presence of TCR and CD28 signaling.
Identifiants
pubmed: 32005952
doi: 10.1038/s41423-020-0361-7
pii: 10.1038/s41423-020-0361-7
pmc: PMC8166953
doi:
Substances chimiques
CD28 Antigens
0
HHLA2 protein, human
0
Immunoglobulins
0
Receptors, Antigen, T-Cell
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1503-1511Références
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