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. Academic Article uri icon

Overview

abstract

  • 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.

publication date

  • October 1, 2014

Research

keywords

  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Cell Differentiation
  • GATA3 Transcription Factor
  • Hematopoietic Stem Cell Transplantation
  • Interleukin-12
  • Signal Transduction
  • T-Box Domain Proteins
  • T-Lymphocyte Subsets

Identity

PubMed Central ID

  • PMC4172137

Scopus Document Identifier

  • 84908209406

Digital Object Identifier (DOI)

  • 10.1111/imm.12304

PubMed ID

  • 24766459

Additional Document Info

volume

  • 143

issue

  • 2