Chronic GVHD (cGVHD) poses a significant risk for HSCT patients. Preclinical development of new therapeutic modalities has been hindered by models with pathologic findings that may not simulate the development of human cGVHD. Previously, we have demonstrated that cGVHD induced by allogeneic HSCT after a conditioning regimen of cyclophosphamide and total-body radiation results in pulmonary dysfu...

Immune cell cosignaling receptors are important modulators of immune cell function. For T cells, cosignaling receptors supply necessary secondary signals supporting activation or attenuation after engagement of antigen-presenting cells. The primary cosignaling receptors belong to either the Ig (CD28-like) or TNF receptor (TNFR) superfamilies. The CD28 family is comprised of coinhibitory and cos...

M cells located in the follicle-associated epithelium of Peyer's patches (PP) are shown to be the principal sites for the sampling of gut luminal antigens. Thus, PP have long been considered the gatekeepers of the mucosal immune system. Here, we report a distinct gateway for the uptake of gut bacteria: clusters of non-follicle-associated epithelium-associated Ulex europaeus agglutinin (UEA)-1(+...

Although the essential role of tumor necrosis factor (TNF) in the control of intracellular bacterial infection is well established, it is uncertain whether the related cytokines lymphotoxin-alpha (LTalpha3) and lymphotoxin-beta (LTbeta) have independent roles in this process. Using C57Bl/6 mice in which the genes for these cytokines have been disrupted, we have examined the relative contributio...

We previously showed that LIGHT and its receptor herpes virus entry mediator (HVEM) are important for development of optimal CD4(+) Th1 cell immunity and resistance to primary Leishmania major infection in mice. In this study, we further characterized the contributions of this molecule in dendritic cell (DC) maturation, initiation, and maintenance of primary immunity and secondary anti-Leishman...

Migraine is classified by the World Health Organization (WHO) as being one of the top 20 most debilitating diseases. According to the neurovascular hypothesis, neuroinflammation may promote the activation and sensitisation of meningeal nociceptors, inducing the persistent throbbing headache characterized in migraine. The tumor necrosis factor (TNF) gene cluster, made up of TNFα, lymphotoxin α (...

Cytokines are important modulators of inflammation and immune responses. Using in situ hybridization with radiolabelled cDNA oligonucleotide probes, we studied the expression of mRNA encoding the cytokines gamma interferon (IFN-gamma), interleukin 4 (IL-4), IL-6, IL-10, transforming growth factor beta (TGF-beta), tumor necrosis factor alpha (TNF-alpha), lymphotoxin, and perforin in mononuclear ...

Neoplastic cells are thought to have defective expression of costimulatory molecules. However, in this study, we show that human melanoma cells express LIGHT/TNFSF14, a ligand of herpesvirus entry mediator on T cells and of lymphotoxin beta receptor on stromal cells. In vitro, melanoma cells stained for LIGHT in the intracellular compartment, with weak or negative cell surface expression. Howev...

A polymorphic (TGCG)n, tetranucleotide repeat was discovered juxtaposed to the (GT)n dinucleotide repeat that comprises the tumor necrosis factor a microsatellite (TNF) located telomeric to the tumor necrosis factor/lymphotoxin gene cluster. The degree of complexity of this compound tetra-,dinucleotide microsatellite consists of 16 potential alleles of combined length ranging from 24 to 54 bp. ...

The TNF locus on chromosome 6p21 encodes a family of proteins with key roles in the immune response whose dysregulation leads to severe disease. Transcriptional regulation is important, with cell type and stimulus-specific enhancer complexes involving the proximal TNF promoter. We show how quantitative chromatin profiling across a 34 kb region spanning the TNF locus has allowed us to identify a...