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

Hegazy, A. N.; Peine, Michael; Helmstetter, Caroline; Panse, Isabel; Frohlich, Anja; Bergthaler, Andréas; Flatz, Lukas; Pinschewer, Daniel; Radbruch, Andreas; Lohning, Max

doi:10.1016/j.immuni.2009.12.004

Scientific article

English

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

Contributors

Hegazy, A. N.; Peine, Michael; Helmstetter, Caroline; Panse, Isabel; Frohlich, Anja; Bergthaler, Andréas; Flatz, Lukas; Pinschewer, Daniel; Radbruch, Andreas; Lohning, Max

Published in

Immunity, vol. 32, no. 1, p. 116-128

Publication date

2010

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/metabolism
Interferon-gamma/ immunology/metabolism
Lymphocyte Activation/ immunology
Lymphocytic choriomeningitis virus/immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
T-Box Domain Proteins/immunology/metabolism
T-Lymphocyte Subsets/ cytology/immunology/metabolism
Th1 Cells/ cytology/immunology/metabolism
Th2 Cells/ cytology/immunology/metabolism

UNIGE affiliation entities

Not a UNIGE publication

Citation (ISO format)

HEGAZY, A. N. et al. Interferons direct Th2 cell reprogramming to generate a stable GATA-3(+)T-bet(+) cell subset with combined Th2 and Th1 cell functions. In: Immunity, 2010, vol. 32, n° 1, p. 116–128. doi: 10.1016/j.immuni.2009.12.004

Article

Identifiers

PID : unige:11295
DOI : 10.1016/j.immuni.2009.12.004
PMID : 20079668

Additional URL for this publication

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Journal ISSN

1074-7613

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Creation

27/08/2010 13:34:43

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27/08/2010 13:34:43

Update

14/03/2023 16:03:32

Status update

14/03/2023 16:03:32

Last indexation

29/10/2024 16:55:06

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

Contributors

Published in

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Abstract

Keywords

UNIGE affiliation entities

Citation (ISO format)

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Technical informations

Creation

First validation

Update

Status update

Last indexation