Ocular immune privilege (IP) limits immune surveillance of intraocular tumors as certain immunogenic tumor cell lines (P815, E.G7-OVA) that are rejected when transplanted in the skin grow progressively when placed in the anterior chamber (a.c.) of the eye. As splenectomy (SPLNX) is known to terminate ocular IP, we characterized immune mechanisms responsible for spontaneous rejection of intraocular tumors in SPLNX mice as a first step toward identifying how to restore tumoricidal activity within the eye. Microarray data showed a 3-fold increase in interferon (IFN)- and a 2.7-fold increase in Fas ligand (FasL). There was a robust increase in transcripts (127 of 408 surveyed) from interferon (IFN)-stimulated genes and a marked decrease (in 40 of 192 surveyed) in the expression of cell-cycle-associated genes. Non-microarray data confirmed that IFN, FasL and CD8+ T cells but not perforin or TNF were required for elimination of intraocular E.G7-OVA tumors that culminated in destruction of the eye (ocular phthsis). IFN and FasL did not target tumor cells directly as the majority of SPLNX IFNR1-/- mice and Fas-defective lpr mice failed to eliminate ocular E.G7-OVA tumors that expressed Fas and IFNR1. Bone marrow chimeras showed that immune cell expression of IFNR1 and Fas was critical and that SPLNX increased the frequency of activated macrophages within ocular tumors in an IFN- and Fas/FasL-dependent manner. Rejection of intraocular tumors was associated with increased ocular mRNA expression of several inflammatory genes including FasL, NOS2, CXCL2 and T-bet. Our data support a model in which IFN- and Fas/FasL-dependent activation of intratumoral macrophage by CD8+ T cells promotes severe intraocular inflammation that indirectly eliminates intraocular tumors by inducing phthisis. The immunosuppressive mechanisms which maintain ocular IP likely interfere with the interaction between CD8+ T cells and macrophage to limit immunosurveillance of intraocular tumors.
Splenectomy promotes indirect elimination of intraocular tumors by CD8+ T cells that is associated with IFNγ- and Fas/FasL-dependent activation of intratumoral macrophages.
Specimen part, Treatment
View SamplesPrion infection in animals results in neurodegeneration and eventually death. To examine the cellular impact of Prion disease, we profiled non-proliferative fully differentiated C2C12 cells, which can replicate prions to high levels. Results suggest that accumulation of high levels of PrPSc in C2C12 myotubes does not cause any overt cellular dysfunction or molecular pathology.
Infectious prions accumulate to high levels in non proliferative C2C12 myotubes.
Specimen part, Cell line, Treatment, Time
View SamplesNuocytes are a recently described cell that responds to both IL-25 and IL-33 and produce high levels of IL-13 and IL-5
Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity.
Specimen part, Time
View SamplesSmall intestine of a pool of three Wt mice and a pool of 3 IL-9tg mice in a balb/c backround.
IL-9- and mast cell-mediated intestinal permeability predisposes to oral antigen hypersensitivity.
No sample metadata fields
View SamplesHow secondary CD4 T cell effectors, derived from resting memory cells, differ from primary cells, derived from nave precursors, and how such differences impact recall responses to pathogens is unknown.
Memory CD4+ T-cell-mediated protection depends on secondary effectors that are distinct from and superior to primary effectors.
Specimen part
View SamplesAims: To assess the virulence of multiple Aeromonas spp. using two models, a neonatal mouse assay and a mouse intestinal cell culture.
Evaluating virulence of waterborne and clinical Aeromonas isolates using gene expression and mortality in neonatal mice followed by assessing cell culture's ability to predict virulence based on transcriptional response.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Adult rat bones maintain distinct regionalized expression of markers associated with their development.
Sex, Specimen part, Treatment
View SamplesPilot study
Adult rat bones maintain distinct regionalized expression of markers associated with their development.
Sex, Specimen part
View SamplesMouse infection with the tapeworm Hymenolepis diminuta leads to a less severe DNBS-colitis. Increased Th2 and regulatory cytokine production in the spleen is a hallmark of Hymenolepis diminuta infection, therefore we hypothesized that given this microenvironment, splenic adaptive cells acquire an anti-inflammatory phenotype. We tested the ability of putative splenic regulatory B cells generated by Hymenolepis diminuta infection to down-regulate intestinal inflammation. We found that unlike splenic B cells from uninfected mice, splenic B cells from Hymenolepis diminuta -infected animals ameliorated chemically-induced colitis.
Splenic B cells from Hymenolepis diminuta-infected mice ameliorate colitis independent of T cells and via cooperation with macrophages.
Specimen part
View SamplesThe TP53 transcription factor is frequently mutated at later stages of epithelial cancers, indicating a possible role in their invasion and metastasis. Importantly, in most cases rather than a simple loss of function p53 mutation, point mutations of p53 accumulate at the protein level and may have dominant negative functions. This study analyses gene expression differences between mice harbouring p53 mutation who do and do not develop metastasis.
Targeting the LOX/hypoxia axis reverses many of the features that make pancreatic cancer deadly: inhibition of LOX abrogates metastasis and enhances drug efficacy.
No sample metadata fields
View Samples