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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.

Original publication

DOI

10.1016/j.immuni.2009.12.004

Type

Journal article

Journal

Immunity

Publication Date

14/01/2010

Volume

32

Pages

116 - 128

Addresses

Experimental Immunology, Department of Rheumatology and Clinical Immunology, Charité - University Medicine Berlin, 10117 Berlin, Germany.

Keywords

T-Lymphocyte Subsets, Th1 Cells, Th2 Cells, Animals, Mice, Inbred C57BL, Mice, Knockout, Mice, Lymphocytic choriomeningitis virus, T-Box Domain Proteins, Cytokines, Adoptive Transfer, Flow Cytometry, Cell Separation, Lymphocyte Activation, Cell Differentiation, GATA3 Transcription Factor, Interferon-gamma