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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
Flatz, Lukas
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Published in Immunity. 2010, vol. 32, no. 1, p. 116-128
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 TransferAnimalsCell Differentiation/ immunologyCell SeparationCytokines/immunologyFlow CytometryGATA3 Transcription Factor/immunology/metabolismInterferon-gamma/ immunology/metabolismLymphocyte Activation/ immunologyLymphocytic choriomeningitis virus/immunologyMiceMice, Inbred C57BLMice, KnockoutT-Box Domain Proteins/immunology/metabolismT-Lymphocyte Subsets/ cytology/immunology/metabolismTh1 Cells/ cytology/immunology/metabolismTh2 Cells/ cytology/immunology/metabolism
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PMID: 20079668
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