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Series GSE4178 Query DataSets for GSE4178
Status Public on Oct 17, 2006
Title Cellular Mechanisms of Fatal Early-Onset Autoimmunity in Mice with the T Cell-Specific Targeting of TGFβ Receptor
Organism Mus musculus
Experiment type Expression profiling by array
Summary Transforming growth factor-β (TGF-β) has been implicated in the control of differentiation and proliferation of multiple cell types. However, a role for TGF-β in the control of immune homeostasis is not fully understood because of its pleiotropic action. Here we report that complete ablation of the TGF-β signaling in T cells engendered aggressive early-onset, multiorgan, autoimmune-associated lesions with 100% mortality. Peripheral CD4+ and CD8+ T cells with TGF-β-receptor II (TGF-βRII) deficiency activated cytolytic and T helper 1 (Th1) differentiation program in a cell-intrinsic T cell receptor (TCR)-specific fashion. Furthermore, TGF-βRII deficiency blocked the development of canonical CD1d-restricted NKT cells. Instead, it facilitated generation of a highly pathogenic T cell subset exhibiting multiple hallmarks of NK cells and sharply elevated amounts of FasL, perforin, granzymes, and interferon-γ. Thus, TGF-β signaling in peripheral T cells is crucial in restraining TCR activation-dependent Th1, cytotoxic, and NK cell-like differentiation program which, when left unchecked, leads to rapidly progressing fatal autoimmunity.
Keywords: Cell type comparison
Overall design To better understand the basis for pathogenicity of TGF-βRII-deficient NK1.1+ T cells, we performed gene expression profiling of NK1.1+ and NK1.1− T cell subsets from Tgfbr2fl/fl x CD4-Cre mice. We limited our analysis to CD8+ T cell subsets because NK1.1+ CD8 T cells made up 70% of total NK1.1+ T cells in Tgfbr2fl/fl x CD4-Cre mice, and this T cell subset showed the greatest numerical increase compared to littermate control mice. Thus, in these experiments we used FACS-sorted NK1.1+ and NK1.1− CD8+ T cells from 15- to 17-day-old mutant mice and total CD8+ T cells from Tgfbr2fl/wt x CD4-Cre littermate controls.

mRNA expression profiles of NK1.1+ and NK1.1− CD8+ T cells from Tgfbr2fl/fl x CD4-Cre (KO) mice were compared to NK1.1− T cells from littermate control Tgfbr2fl/WT x CD4-Cre (Control) mice.
Contributor(s) Marie JC, Liggit D, Rudensky AY
Citation(s) 16973387
Submission date Feb 03, 2006
Last update date Feb 11, 2019
Contact name Jeffrey Rasmussen
Phone 2065439058
Organization name University of Washington
Department Immunology
Lab Rudensky
Street address
City Seattle
State/province WA
ZIP/Postal code 98195
Country USA
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (3)
GSM95587 NK1.1 plus TGFbeta RII KO T cells KO_NKT
GSM95588 NK1.1 minus TGFbeta RII KO T cells T_KO
GSM95589 NK1.1 minus control T cells T_WT
BioProject PRJNA94981

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