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Insufficient interleukin‐12 signalling favours differentiation of human CD4 + and CD 8 + T cells into GATA ‐3 + and GATA ‐3 + T‐bet + subsets in humanized mice
Author(s) -
Billerbeck Eva,
Labitt Rachael N.,
Vega Kevin,
FriasStaheli Natalia,
Dorner Marcus,
Xiao Jing W.,
Rice Charles M.,
Ploss Alexander
Publication year - 2014
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12304
Subject(s) - cd8 , biology , microbiology and biotechnology , immune system , phenotype , interleukin 3 , transcription factor , cytotoxic t cell , interleukin 4 , t cell , cellular differentiation , dendritic cell , immunology , in vitro , interleukin 21 , gene , genetics
Summary Differentiation of CD 4 + 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 + CD 4 + 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 CD 4 + and, notably, CD 8 + 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 CD 4 + and CD 8 + 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.