Cloned CD4 T cell lines that recognize the Ac1-16 peptide of myelin basic protein bound to I-Au were isolated and used analyze immunopathogenesis experimental autoimmune encephalomyelitis (EAE). helper type 1 (Th1) clones induced disease, while Th2 did not. Using variants a single cloned Th1 line, surface expression alpha 4 integrins (very late antigen [VLA-4]) was identified as major pathogenic factor. Encephalitogenic nonencephalitogenic differ by 10-fold in their level integrin ability...

Uncertainty regarding pathogenic mechanisms has been a major impediment to effective prevention and treatment for human neurologic diseases such as multiple sclerosis, tropical spastic paraparesis, AIDS demyelinating disease. Here, we implicate lymphotoxin (LT) (tumor necrosis factor beta [TNF-beta]) TNF-alpha in experimental allergic encephalomyelitis (EAE), murine model of an autoimmune In this communication, report that recipient mice with antibody neutralizes LT prevents transfer...

Lymphotoxin α (LTα)–deficient mice revealed critical roles for LTα in lymphoid organogenesis, but it is not clear whether functions through an homotrimer (LTα3) or LTα/β heterotrimers. We generated LTβ-deficient and found them to lack Peyer's patches, peripheral lymph nodes, splenic germinal centers, follicular dendritic cells. Unlike LTα-deficient mice, had cervical mesenteric nodes. Furthermore, the nodes center–like regions, although these structures appeared The absence of yet their...

In presenting a unifying concept for chronic inflammation and lymphoid organogenesis, we suggest that lymphotoxin's (LT, LT-alpha, TNF-beta) crucial role in these processes is pivotal similar. Chronic inflammatory lesions developed the kidney pancreas at sites of transgene expression rat insulin promoter-LT (RIP-LT) mice resembled lymph nodes with regard to cellular composition (T cells, B plasma antigen-presenting cells), delineated T cell areas, primary secondary follicles, characteristic...

mAb to murine TNF (MuTNF) were produced after immunization of Armenian hamsters with purified, Escherichia coli-derived rMuTNF-alpha. Antibody from clone TN3-19.12, was purified and found inhibit 100% the lytic activity either recombinant or natural MuTNF-alpha at an antibody input 25 ng/U. TN3-19.12 also inhibited all in culture supernatants a variety T cell sources, including activated clones hybridomas (all which expressed high levels TNF-alpha TNF-beta (lymphotoxin, LT) mRNA). Western...

The cytopathic effect of lymph node cells from tuberculin-sensitized rats on rat embryo fibroblasts in the presence PPD was not enhanced by admixture normal (nonsensitized) cells. Preincubation studies showed that this vitro response is initiated reaction lymphocytes with specific antigen, beginning within 30 min, rather than uptake antigen fibroblasts. supernatant fluids suspensions sensitized incubated for 17 hr or more possessed cytotoxic activity. target a marked increase acid...

To trigger an effective immune response, antigen and antigen-presenting cells travel to the lymph nodes via collecting lymphatic vessels. However, our understanding of regulation vessel function transport is limited. dissect molecular control function, we developed a unique mouse model that allows intravital imaging autonomous contraction. Using this method, demonstrated endothelial nitric oxide synthase (eNOS) in required for robust contractions under physiological conditions. By contrast,...

Among the most consequential unknowns of devastating COVID-19 pandemic are durability immunity and time to likely reinfection. There limited direct data on SARS-CoV-2 long-term immune responses The aim this study is use among evolutionarily close coronavirus relatives estimate times reinfection by a comparative evolutionary analysis related viruses SARS-CoV, MERS-CoV, human (HCoV)-229E, HCoV-OC43, HCoV-NL63.We conducted phylogenetic analyses S, M, ORF1b genes reconstruct maximum-likelihood...

To study the role of CD40 ligand (CD40L) in host immune responses against intracellular pathogens, we infected CD40L knockout (CD40L−/−) mice with Leishmania amazonensis. Although wild-type were susceptible to infection and developed progressive ulcerative lesions, tissue parasite burdens CD40L−/− significantly higher. This heightened susceptibility was associated an impaired T cell macrophage activation altered inflammatory response, as reflected by low levels IFNγ, lymphotoxin–tumor...

Platelet/endothelial cell adhesion molecule-1 (PECAM-1, CD31), a 130-kDa glycoprotein member of the Ig superfamily transmembrane proteins, is expressed on endothelial cells, platelets, and subsets leukocytes. It functions as molecule well scaffolding capable modulating cellular signaling pathways. In this study, using PECAM-1–deficient (KO) mice, cells derived from these we demonstrate that absence PECAM-1 expression associated with an early onset clinical symptoms during experimental...

Lymphokine activity in seven myelin basic protein (MBP)-specific T cell clones was examined. All of the recognize MBP peptide 1–9 context I-Au. A strong positive correlation found between levels lymphotoxin (LT) and tumor necrosis factor alpha (TNF-α) mRNA biological on L929 cells their capacity to Induce paralysis, clinical hallmark experimental allergic encephalomyelitls (EAE). No interleukin-2 or gamma interferon production encephalitogenicity. LT and/or TNF-α may play a central role...

Platelet/endothelial cell adhesion molecule-1 (PECAM-1, CD31), a 130-kDa glycoprotein member of the Ig superfamily transmembrane proteins, is expressed on endothelial cells, platelets, and subsets leukocytes. It functions as molecule well scaffolding capable modulating cellular signaling pathways. In this study, using PECAM-1–deficient (KO) mice, cells derived from these we demonstrate that absence PECAM-1 expression associated with an early onset clinical symptoms during experimental...

Lymph node (LN) function depends on T and B cell compartmentalization, antigen presenting cells, high endothelial venules (HEVs) expressing mucosal addressin adhesion molecule (MAdCAM-1) peripheral (PNAd), ligands for naive entrance into LNs. Luminal PNAd expression requires a HEV-restricted sulfotransferase (HEC-6ST). To investigate LTαβ's activities in lymphoid organogenesis, mice simultaneously LTα LTβ under rat insulin promoter II (RIP) control were compared with RIPLTα model of...

In the presence of specific antigen, lymph node cells from inbred rats with delayed hypersensitivity to tuberculoprotein, bovine gammaglobulin, and egg albumin produced progressive destruction monolayers rat embryo fibroblasts in tissue culture, first apparent at 48 hr maximal 72 hr. The effect was did not depend on a genetic difference between target cells. It required antigen concentrations equal or greater than 1.25 µg/ml lymphocyte: cell ratios approximately 10 20:1. could be evaluated...

Prions typically accumulate in nervous and lymphoid tissues. Because proinflammatory cytokines immune cells are required for prion replication, we tested whether inflammatory conditions affect pathogenesis. We administered prions to mice with five diseases of the kidney, pancreas, or liver. In all cases, chronic lymphocytic inflammation enabled accumulation otherwise prion-free organs. Inflammatory foci consistently correlated lymphotoxin up-regulation ectopic induction FDC-M1 + expressing...

The lymphotoxin (LT)/tumor necrosis factor (TNF) family has been implicated in the neurologic inflammatory diseases multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE). To determine role of individual members EAE, C57BL/6 mice, LT-α–deficient (LT-α−/− mice), or LT-β–deficient (LT-β−/− their wild-type (WT) littermates were immunized with rat myelin oligodendrocyte glycoprotein (MOG) peptide 35-55. WT mice developed chronic, sustained paralytic disease average maximum...

Abstract The mature phenotype of peripheral lymph node (LN) high endothelial venules (HEVs), defined as MAdCAM-1lowPNAdhighLTβRhigh HEC-6SThigh, is dependent on signaling through the lymphotoxin-β receptor (LTβR). Plasticity PLN HEVs during immunization with oxazolone was apparent a reversion to an immature (MAdCAM-1highPNAdlowLTβRlow HEC-6STlow) followed by recovery phenotype. B cells and inhibited LTβR-Ig treatment. Concurrent HEV reversion, at day 4 following or OVA immunization, reduced...

Lymph node cells from inbred rats having delayed sensitivity to soluble proteins inhibit growth of syngeneic or allogeneic fibroblasts in the presence specific antigen. A relation is suggested between this vitro phenomenon and other systems believed be manifestations hypersensitivity.