Insufficient interleukin-12 signalling favours differentiation of human CD4+ and CD8+ T cells into GATA-3+ and GATA-3+ T-bet+ subsets in humanized mice

Eva K. Billerbeck, Rachael N. Labitt, Kevin Vega, Natalia Frias-Staheli, Marcus Dorner, Jing W. Xiao, Charles M. Rice, Alexander Ploss

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Summary: Differentiation of CD4+ T cells into type 1 or type 2 subsets is mediated by the expression of the opposing lineage defining transcription factors T-bet and GATA-3. However, the existence of GATA-3+ T-bet+ CD4+ T cells in mice suggests functional plasticity of these subsets. Little is known about type 1 and type 2 plasticity of human T-cell subsets in vivo. Here, we show that in the xenogeneic environment of humanized mice, which lacks a functional immune-regulatory network, human CD4+ and, notably, CD8+ T cells preferentially differentiate into interleukin (IL)-4+ GATA-3+ and IL-4+ interferon-γ+ GATA-3+ T-bet+ subsets. Treatment with recombinant human IL-12 or expansion of IL-12-producing human dendritic cells in vivo reverted this phenotype and led to the down-regulation of GATA-3 expression. These changes also correlated with improved antiviral immune responses in humanized mice. In conclusion, our study shows the capacity of human CD4+ and CD8+ T cells for stable co-expression of GATA-3 and T-bet in humanized mice and reveals a critical role for IL-12 in regulating this phenotype.

Original languageEnglish (US)
Pages (from-to)202-218
Number of pages17
JournalImmunology
Volume143
Issue number2
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

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Interleukin-12
T-Lymphocytes
Interleukin-4
GATA Transcription Factors
Phenotype
T-Lymphocyte Subsets
Dendritic Cells
Interferons
Antiviral Agents
Down-Regulation

Keywords

  • Humanized mice
  • Interleukin-12
  • T-cell plasticity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Insufficient interleukin-12 signalling favours differentiation of human CD4+ and CD8+ T cells into GATA-3+ and GATA-3+ T-bet+ subsets in humanized mice. / Billerbeck, Eva K.; Labitt, Rachael N.; Vega, Kevin; Frias-Staheli, Natalia; Dorner, Marcus; Xiao, Jing W.; Rice, Charles M.; Ploss, Alexander.

In: Immunology, Vol. 143, No. 2, 01.01.2014, p. 202-218.

Research output: Contribution to journalArticle

Billerbeck, Eva K. ; Labitt, Rachael N. ; Vega, Kevin ; Frias-Staheli, Natalia ; Dorner, Marcus ; Xiao, Jing W. ; Rice, Charles M. ; Ploss, Alexander. / Insufficient interleukin-12 signalling favours differentiation of human CD4+ and CD8+ T cells into GATA-3+ and GATA-3+ T-bet+ subsets in humanized mice. In: Immunology. 2014 ; Vol. 143, No. 2. pp. 202-218.
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