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

Autor:	Marcus Dorner, Rachael N. Labitt, Natalia Frias-Staheli, Eva Billerbeck, Jing W. Xiao, Alexander Ploss, Kevin Vega, Charles M. Rice
Rok vydání:	2014
Předmět:	CD4-Positive T-Lymphocytes Transplantation Heterologous Immunology Mice Transgenic GATA3 Transcription Factor Mice SCID CD8-Positive T-Lymphocytes Biology Adenoviridae Interferon-gamma Mice Immune system Mice Inbred NOD T-Lymphocyte Subsets In vivo Animals Humans Immunology and Allergy Cytotoxic T cell Cell Lineage Transcription factor Cells Cultured Mice Inbred BALB C Hematopoietic Stem Cell Transplantation Interleukin Cell Differentiation Original Articles Dendritic Cells Viral Load Interleukin-12 Phenotype Cell biology Mice Inbred C57BL Kinetics Liver Host-Pathogen Interactions Interleukin 12 Interleukin-4 T-Box Domain Proteins Injections Intraperitoneal CD8 Signal Transduction
Zdroj:	Immunology. 143:202-218
ISSN:	0019-2805
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5b558c1b926b433f7dd1bb0133331c4b https://doi.org/10.1111/imm.12304 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.