A distinct CD38+CD45RA+ population of CD4+, CD8+, and double-negative T cells is controlled by FAS.
ADP-ribosyl Cyclase 1
/ immunology
Adolescent
Adult
Aged
CD4-Positive T-Lymphocytes
/ immunology
CD8-Positive T-Lymphocytes
/ immunology
Child
Child, Preschool
Female
Humans
Infant
Infant, Newborn
Leukocyte Common Antigens
/ metabolism
Lymphocyte Activation
/ immunology
Lymphoproliferative Disorders
/ immunology
Male
Middle Aged
Signal Transduction
/ immunology
Young Adult
fas Receptor
/ immunology
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
01 02 2021
01 02 2021
Historique:
received:
20
11
2019
revised:
06
08
2020
accepted:
09
10
2020
entrez:
10
11
2020
pubmed:
11
11
2020
medline:
10
9
2021
Statut:
ppublish
Résumé
The identification and characterization of rare immune cell populations in humans can be facilitated by their growth advantage in the context of specific genetic diseases. Here, we use autoimmune lymphoproliferative syndrome to identify a population of FAS-controlled TCRαβ+ T cells. They include CD4+, CD8+, and double-negative T cells and can be defined by a CD38+CD45RA+T-BET- expression pattern. These unconventional T cells are present in healthy individuals, are generated before birth, are enriched in lymphoid tissue, and do not expand during acute viral infection. They are characterized by a unique molecular signature that is unambiguously different from other known T cell differentiation subsets and independent of CD4 or CD8 expression. Functionally, FAS-controlled T cells represent highly proliferative, noncytotoxic T cells with an IL-10 cytokine bias. Mechanistically, regulation of this physiological population is mediated by FAS and CTLA4 signaling, and its survival is enhanced by mTOR and STAT3 signals. Genetic alterations in these pathways result in expansion of FAS-controlled T cells, which can cause significant lymphoproliferative disease.
Identifiants
pubmed: 33170215
pii: 211525
doi: 10.1084/jem.20192191
pmc: PMC7658692
pii:
doi:
Substances chimiques
fas Receptor
0
Leukocyte Common Antigens
EC 3.1.3.48
ADP-ribosyl Cyclase 1
EC 3.2.2.6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2020 Maccari et al.
Déclaration de conflit d'intérêts
Disclosures: S. Fuchs reported being an employee of F. Hoffmann-La Roche (Roche) AG. F.G. Kapp reported personal fees from Novartis outside the submitted work. M.G. Seidel reported personal fees from Jazz Pharmaceuticals, personal fees from Shire, personal fees from Novartis, and personal fees from Amgen outside the submitted work. T. Kalina reported being a Scientific Board member of Scailyte AG. B. Grimbacher reported personal fees from University Hospital Freiburg, personal fees from Pharmaceutical companies, personal fees from Diagnostic companies, grants from Pharmaceutical companies, and grants from Public funding agencies outside the submitted work. A.P. Frei reported being an employee of F. Hoffmann-La Roche (Roche) AG. S. Ehl reported grants from UCB outside the submitted work. No other disclosures were reported.
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