Measuring Thymic Clonal Deletion at the Population Level.
Animals
Antigen Presentation
Apoptosis
Autoantigens
/ immunology
Bone Marrow Cells
/ immunology
CD28 Antigens
/ metabolism
Caspase 3
/ metabolism
Cells, Cultured
Clonal Deletion
Mice
Mice, Inbred C57BL
Mice, Transgenic
Proteolysis
Receptors, Antigen, T-Cell
/ metabolism
Receptors, CCR7
Signal Transduction
Thymus Gland
/ immunology
Journal
Journal of immunology (Baltimore, Md. : 1950)
ISSN: 1550-6606
Titre abrégé: J Immunol
Pays: United States
ID NLM: 2985117R
Informations de publication
Date de publication:
01 06 2019
01 06 2019
Historique:
received:
14
02
2019
accepted:
25
03
2019
pubmed:
24
4
2019
medline:
27
2
2020
entrez:
24
4
2019
Statut:
ppublish
Résumé
Clonal deletion of T cells specific for self-antigens in the thymus has been widely studied, primarily by approaches that focus on a single receptor (using TCR transgenes) or a single specificity (using peptide-MHC tetramers). However, less is known about clonal deletion at the population level. In this article, we report an assay that measures cleaved caspase 3 to define clonal deletion at the population level. This assay distinguishes clonal deletion from apoptotic events caused by neglect and approximates the anatomic site of deletion using CCR7. This approach showed that 78% of clonal deletion events occur in the cortex in mice. Medullary deletion events were detected at both the semimature and mature stages, although mature events were associated with failed regulatory T cell induction. Using this assay, we showed that bone marrow-derived APC drive approximately half of deletion events at both stages. We also found that both cortical and medullary deletion rely heavily on CD28 costimulation. These findings demonstrate a useful strategy for studying clonal deletion within the polyclonal repertoire.
Identifiants
pubmed: 31010850
pii: jimmunol.1900191
doi: 10.4049/jimmunol.1900191
pmc: PMC6529273
mid: NIHMS1525874
doi:
Substances chimiques
Autoantigens
0
CD28 Antigens
0
Ccr7 protein, mouse
0
Receptors, Antigen, T-Cell
0
Receptors, CCR7
0
Caspase 3
EC 3.4.22.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
3226-3233Subventions
Organisme : NIAID NIH HHS
ID : T32 AI007313
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA077598
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI035296
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI039560
Pays : United States
Organisme : NIAID NIH HHS
ID : F30 AI131483
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008244
Pays : United States
Informations de copyright
Copyright © 2019 by The American Association of Immunologists, Inc.
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