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
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 08, 2014
- Source ID
- 10.1111/imm.12304
Entities
People
- Alexander Ploss
- Charles M. Rice
- Eva Billerbeck
- Jing W. Xiao
- Kevin Vega
- Marcus Dorner
- Natalia Frias‐staheli
- Rachael N. Labitt
Organizations
- American Liver Foundation
- Gates Foundation
- German Research Foundation
- Greenberg Medical Research Institute
- Infectious Diseases Society of America
- National Institutes of Health
- The Rockefeller University
- Walter Reed Army Institute of Research