Roles of T Follicular Helper Cells and T Follicular Regulatory Cells in Autoantibody Production in IL-2-Deficient Mice.
Animals
Autoantibodies
/ biosynthesis
Autoimmunity
/ immunology
Cell Differentiation
Gene Knockout Techniques
Interleukin-2
/ genetics
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Models, Animal
Myeloid Differentiation Factor 88
/ genetics
Proto-Oncogene Proteins c-bcl-6
/ genetics
T-Lymphocytes, Helper-Inducer
/ immunology
T-Lymphocytes, Regulatory
/ immunology
Journal
ImmunoHorizons
ISSN: 2573-7732
Titre abrégé: Immunohorizons
Pays: United States
ID NLM: 101708159
Informations de publication
Date de publication:
12 07 2019
12 07 2019
Historique:
received:
24
04
2019
accepted:
27
06
2019
entrez:
30
7
2019
pubmed:
30
7
2019
medline:
27
2
2020
Statut:
epublish
Résumé
Autoantibodies can result from excessive T follicular helper (Tfh) cell activity, whereas T follicular regulatory (Tfr) cells negatively regulate autoantibody production. IL-2 knockout (KO) mice on the BALB/c background have elevated Tfh responses, produce autoantibodies, and develop lethal autoimmunity. We analyzed Tfh and Tfr cells in IL-2 KO mice on the C57BL/6 (B6) genetic background. In B6 IL-2 KO mice, the spontaneous formation of Tfh cells and germinal center B cells was greatly enhanced, along with production of anti-DNA autoantibodies. IL-2 has been reported to repress Tfr cell differentiation; however, Tfr cells were not increased over wild-type levels in the B6 IL-2 KO mice. To assess Tfh and Tfr cell regulation of autoantibody production in IL-2 KO mice, we generated IL-2 KO mice with a T cell-specific deletion of the master Tfh cell transcription factor Bcl6. In IL-2 KO Bcl6 conditional KO (2KO-Bcl6TC) mice, Tfh cells, Tfr cells, and germinal center B cells were ablated. In contrast to expectations, autoantibody IgG titers in 2KO-Bcl6TC mice were significantly elevated over autoantibody IgG titers in IL-2 KO mice. Specific deletion of Tfr cells with Foxp3-cre Bcl6-flox alleles in IL-2 KO mice led to early lethality, before high levels of autoantibodies could develop. We found IL-2
Identifiants
pubmed: 31356160
pii: 3/7/306
doi: 10.4049/immunohorizons.1900034
pmc: PMC7144868
mid: NIHMS1575088
doi:
Substances chimiques
Autoantibodies
0
Bcl6 protein, mouse
0
Interleukin-2
0
Myd88 protein, mouse
0
Myeloid Differentiation Factor 88
0
Proto-Oncogene Proteins c-bcl-6
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
306-316Subventions
Organisme : NIAID NIH HHS
ID : R01 AI132771
Pays : United States
Organisme : NIDDK NIH HHS
ID : U54 DK106846
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA082709
Pays : United States
Informations de copyright
Copyright © 2019 The Authors.
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