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.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Humanized mice
- T-cell plasticity