@article{85456,
  keywords = {Animals, Kinetics, Humans, signal transduction, Phenotype, Mice, Mice, Inbred C57BL, Host-Pathogen Interactions, Cells, Cultured, Mice, Transgenic, Cell Differentiation, Cell Lineage, Interferon-gamma, Adenoviridae, Liver, Mice, Inbred BALB C, T-Box Domain Proteins, Mice, SCID, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Dendritic Cells, GATA3 Transcription Factor, Hematopoietic Stem Cell Transplantation, Injections, Intraperitoneal, Interleukin-12, Interleukin-4, Mice, Inbred NOD, T-Lymphocyte Subsets, Transplantation, Heterologous, Viral Load},
  author = {Eva Billerbeck and Rachael Labitt and Kevin Vega and Natalia Frias-Staheli and Marcus Dorner and Jing Xiao and Charles Rice and Alexander Ploss},
  title = {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.},
  abstract = {<p>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.</p>
},
  year = {2014},
  journal = {Immunology},
  volume = {143},
  pages = {202-18},
  month = {10/2014},
  issn = {1365-2567},
  doi = {10.1111/imm.12304},
  language = {eng},
}