T-bet optimizes CD4 T-cell responses against influenza through CXCR3-dependent lung trafficking but not functional programming.
Animals
CD4-Positive T-Lymphocytes
/ immunology
Cytokines
/ metabolism
Disease Models, Animal
Disease Resistance
/ genetics
Gene Expression
Host-Pathogen Interactions
/ immunology
Influenza A virus
/ immunology
Lung
/ immunology
Mice
Mice, Knockout
Orthomyxoviridae Infections
/ immunology
Receptors, CXCR3
/ metabolism
Signal Transduction
T-Box Domain Proteins
/ genetics
T-Lymphocyte Subsets
/ immunology
T-Lymphocytes, Helper-Inducer
/ immunology
Journal
Mucosal immunology
ISSN: 1935-3456
Titre abrégé: Mucosal Immunol
Pays: United States
ID NLM: 101299742
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
10
01
2019
accepted:
04
06
2019
revised:
09
05
2019
pubmed:
7
7
2019
medline:
21
4
2020
entrez:
7
7
2019
Statut:
ppublish
Résumé
Although clearance of many intracellular pathogens requires T-bet-dependent CD4 T cell programming, the extent to which T-bet is needed to direct protective CD4 responses against influenza is not known. Here, we characterize wild-type and T-bet-deficient CD4 cells during murine influenza infection. Surprisingly, although T-bet expression has broad impacts on cytokine production by virus-specific CD4 cells, the protective efficacy of T-bet-deficient effector cells is only marginally reduced. This reduction is due to lower CXCR3 expression, leading to suboptimal accumulation of activated T-bet-deficient cells in the infected lung. However, T-bet-deficient cells outcompete wild-type cells to form lung-resident and circulating memory populations following viral clearance, and primed T-bet-deficient mice efficiently clear supralethal heterosubtypic influenza challenges even when depleted of CD8 T cells. These results are relevant to the identification of more incisive correlates of protective T cells and for vaccines that aim to induce durable cellular immunity against influenza.
Identifiants
pubmed: 31278374
doi: 10.1038/s41385-019-0183-z
pii: S1933-0219(22)00444-5
pmc: PMC6717559
mid: NIHMS1531969
doi:
Substances chimiques
CXCR3 protein, human
0
Cytokines
0
Receptors, CXCR3
0
T-Box Domain Proteins
0
T-box transcription factor TBX21
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
1220-1230Subventions
Organisme : NIAID NIH HHS
ID : R21 AI117457
Pays : United States
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