STEP (striatal-enriched tyrosine phosphatase) is a brain-specific phosphatase named for its robust expression in striatum. Brains from homozygous and heterozygous STEP knockout mice and wild-type littermates were harvested, and striatum microdissected. RNA was extracted and hybridized to Affymetrix 230_2 microarray chips.
Downstream effects of striatal-enriched protein tyrosine phosphatase reduction on RNA expression in vivo and in vitro.
Sex, Specimen part, Treatment
View SamplesWe used gene expression microarrays to identify genes whose expression was influenced differently by TNFa in Fancc-deficient mice compared to wild type (WT) mice. To identify genes whose expression was directly or indirectly influenced by Fancc, we looked in particular for genes either suppressed or induced by TNF in WT cells that were not affected by TNF in Fancc-deficient cells.
FANCL ubiquitinates β-catenin and enhances its nuclear function.
Specimen part
View SamplesCD4+ T cell help is critical for optimal CD8+ T cell expansion after priming in many experimental systems. However, a role for CD4+ T cells in regulating the initial steps of CD8+ T cell effector differentiation is not well established. Here we demonstrate that absence of CD4+ T cells at the time of replication-incompetent adenovirus vector immunization of C57BL/6 mice led to immediate CD8+ T cell dysfunction characteristic of exhaustion at the first detectable timepoints as well as impaired expansion of antigen-specific CD8+ T cells. The absence of CD4+ T cell help resulted in antigen-specific CD8+ T cells that had reduced ex vivo cytotoxicity and decreased capacity to produce IFN- and TNF-. CD8+ T cells primed in the absence of CD4+ T cells expressed elevated levels of the inhibitory receptors PD-1, LAG-3, and Tim-3, and these cells exhibited transcriptomic exhaustion profiles by gene set enrichment analysis. This dysfunctional state was imprinted within 3 days of immunization and could not be reversed by provision of CD4+ T cell help after priming. Partial rescue of unhelped CD8+ T cell expansion and effector differentiation could be achieved by PD-1 pathway blockade or recombinant IL-2 administration.
Immediate Dysfunction of Vaccine-Elicited CD8+ T Cells Primed in the Absence of CD4+ T Cells.
Specimen part, Time
View Samples