B7-CD28 co-stimulation modulates central tolerance via thymic clonal deletion and Treg generation through distinct mechanisms.
Animals
Antigen-Presenting Cells
/ metabolism
Autoimmunity
/ physiology
B7-1 Antigen
/ metabolism
CD28 Antigens
/ genetics
Cell Differentiation
/ immunology
Central Tolerance
Clonal Deletion
Encephalomyelitis, Autoimmune, Experimental
/ immunology
Flow Cytometry
Gene Knock-In Techniques
Mice
Mice, Knockout
Receptors, Antigen, T-Cell, alpha-beta
/ genetics
Signal Transduction
/ immunology
T-Lymphocytes, Regulatory
/ immunology
Thymocytes
/ physiology
Thymus Gland
/ cytology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
08 12 2020
08 12 2020
Historique:
received:
01
03
2020
accepted:
09
11
2020
entrez:
9
12
2020
pubmed:
10
12
2020
medline:
8
1
2021
Statut:
epublish
Résumé
The molecular and cellular mechanisms mediating thymic central tolerance and prevention of autoimmunity are not fully understood. Here we show that B7-CD28 co-stimulation and B7 expression by specific antigen-presenting cell (APC) types are required for clonal deletion and for regulatory T (Treg) cell generation from endogenous tissue-restricted antigen (TRA)-specific thymocytes. While B7-CD28 interaction is required for both clonal deletion and Treg induction, these two processes differ in their CD28 signaling requirements and in their dependence on B7-expressing dendritic cells, B cells, and thymic epithelial cells. Meanwhile, defective thymic clonal deletion due to altered B7-CD28 signaling results in the accumulation of mature, peripheral TRA-specific T cells capable of mediating destructive autoimmunity. Our findings thus reveal a function of B7-CD28 co-stimulation in shaping the T cell repertoire and limiting autoimmunity through both thymic clonal deletion and Treg cell generation.
Identifiants
pubmed: 33293517
doi: 10.1038/s41467-020-20070-x
pii: 10.1038/s41467-020-20070-x
pmc: PMC7722925
doi:
Substances chimiques
B7-1 Antigen
0
CD28 Antigens
0
Receptors, Antigen, T-Cell, alpha-beta
0
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
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