Interferons direct Th2 cell reprogramming to generate a stable GATA-3(+)T-bet(+) cell subset with combined Th2 and Th1 cell functions.

Details

Serval ID
serval:BIB_15FE5057A3AB
Type
Article: article from journal or magazin.
Collection
Publications
Title
Interferons direct Th2 cell reprogramming to generate a stable GATA-3(+)T-bet(+) cell subset with combined Th2 and Th1 cell functions.
Journal
Immunity
Author(s)
Hegazy A.N., Peine M., Helmstetter C., Panse I., Fröhlich A., Bergthaler A., Flatz L., Pinschewer D.D., Radbruch A., Löhning M.
ISSN
1097-4180 (Electronic)
ISSN-L
1074-7613
Publication state
Published
Issued date
2010
Volume
32
Number
1
Pages
116-128
Language
english
Abstract
Current T cell differentiation models invoke separate T helper 2 (Th2) and Th1 cell lineages governed by the lineage-specifying transcription factors GATA-3 and T-bet. However, knowledge on the plasticity of Th2 cell lineage commitment is limited. Here we show that infection with Th1 cell-promoting lymphocytic choriomeningitis virus (LCMV) reprogrammed otherwise stably committed GATA-3(+) Th2 cells to adopt a GATA-3(+)T-bet(+) and interleukin-4(+)interferon-gamma(+) "Th2+1" phenotype that was maintained in vivo for months. Th2 cell reprogramming required T cell receptor stimulation, concerted type I and type II interferon and interleukin-12 signals, and T-bet. LCMV-triggered T-bet induction in adoptively transferred virus-specific Th2 cells was crucial to prevent viral persistence and fatal immunopathology. Thus, functional reprogramming of unfavorably differentiated Th2 cells may facilitate the establishment of protective immune responses. Stable coexpression of GATA-3 and T-bet provides a molecular concept for the long-term coexistence of Th2 and Th1 cell lineage characteristics in single memory T cells.
Keywords
Adoptive Transfer, Animals, Cell Differentiation/immunology, Cell Separation, Cytokines/immunology, Flow Cytometry, GATA3 Transcription Factor/immunology, GATA3 Transcription Factor/metabolism, Interferon-gamma/immunology, Interferon-gamma/metabolism, Lymphocyte Activation/immunology, Lymphocytic choriomeningitis virus/immunology, Mice, Mice, Inbred C57BL, Mice, Knockout, T-Box Domain Proteins/immunology, T-Box Domain Proteins/metabolism, T-Lymphocyte Subsets/cytology, T-Lymphocyte Subsets/immunology, Th1 Cells/cytology, Th1 Cells/immunology, Th2 Cells/cytology, Th2 Cells/immunology
Pubmed
Open Access
Yes
Create date
23/03/2012 18:29
Last modification date
20/08/2019 12:45
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