AbstractThe Epstein-Barr virus (EBV) transforming protein LMP1 appears to be a constitutively activated tumor necrosis factor receptor (TNFR) on the basis of an intrinsic ability aggregate in plasma membrane and association its cytoplasmic carboxyl terminus (CT) with TNFR-associated factors (TRAFs). We now show that EBV-transformed B lymphocytes most TRAF1 or TRAF3 5% TRAF2 are associated is TRAF3. TRAF1, TRAF2, bind single site CT corresponding amino acids (aa) 199 214, within domain which...

We have isolated a cDNA encoding novel hematopoietin receptor family member related to the p40 subunit of interleukin-12 and ciliary neurotrophic factor receptor, whose expression is induced in B lymphocytes by Epstein-Barr virus (EBV) infection. This gene, which we designated EBV-induced gene 3 (EBI3), encodes 34-kDa glycoprotein lacks membrane-anchoring motif secreted. Despite absence cysteines likely mediate covalent linkage an integral membrane protein, EBI3 also present on plasma...

Production by endothelial cells of the regulated on activation normal T expressed and secreted chemokine (RANTES) has recently been evidenced during delayed-type hypersensitivity (DTH) reactions may contribute to local accumulation macrophages CD4+ memory lymphocytes. To document mechanism inducing RANTES production in this condition, we analyzed effect cytokines known influence formation DTH granulomas. Little or no was produced after stimulation HUVEC with IFN-gamma, IL-1 beta, TNF-alpha....

The Epstein-Barr virus-induced gene 3 (EBI3) is a novel soluble hematopoietin component related to the p40 subunit of interleukin 12 (IL-12). When EBI3 was expressed in cells, it accumulated endoplasmic reticulum and associated with molecular chaperone calnexin, indicating that subsequent processing secretion might be dependent on association second subunit. Coimmunoprecipitations from lysates culture media cells transfected expression vectors for and/or p35 IL-12 now reveal specific p35....

Abstract BCMA (B cell maturation) is a nonglycosylated integral membrane type I protein that preferentially expressed in mature B lymphocytes. Previously, we reported human malignant myeloma line not primarily present on the surface but lies perinuclear structure partially overlaps Golgi apparatus. We now show transiently or stably transfected cells, located surface, as well perinulear Golgi-like structure. also overexpression of 293 cells activates NF-κB, Elk-1, c-Jun N-terminal kinase, and...

Latent infection membrane protein 1 (LMP1), the Epstein-Barr virus transforming protein, associates with tumor necrosis factor receptor (TNFR) associated (TRAF1) and TRAF3. Since TRAF2 has been implicated in TNFR-mediated NF-kappa B activation, we have evaluated role of LMP1-mediated activation. binds vitro to LMP1 carboxyl-terminal cytoplasmic domain (CT), coprecipitates lymphoblasts, relocalizes plasma patches. A dominant negative deletion mutant that lacks amino acids 6-86 (TRAF/ delta...

ABSTRACT In this study, we investigated the induction of cellular gene expression by Epstein-Barr Virus (EBV) latent membrane protein 1 (LMP1). Previously, LMP1 was shown to induce ICAM-1, LFA-3, CD40, and EBI3 in EBV-negative Burkitt lymphoma (BL) cells epidermal growth factor receptor (EGF-R) epithelial cells. We now show that also increased Fas tumor necrosis receptor-associated (TRAF1) BL mediates NF-κB activation via two independent domains located its C-terminal cytoplasmic tail, a...

To understand the selective accumulation of memory T helper lymphocytes and macrophages in delayed-type hypersensitivity (DTH) granulomas, we studied situ production RANTES, a chemokine initially characterized on basis its vitro chemotactic properties for each these cell populations. RANTES gene expression was by hybridization 15 human lymph nodes presenting typical DTH lesions related to either sarcoidosis or tuberculosis. A positive signal detected all cases. Labeling specific lesions, as...

The abilities of the different cells from human central nervous system (CNS) to produce IL-6, IL-1 beta, and TNF-alpha were tested in vitro using either cultures enriched embryonic microglial or primary CNS cells. High amounts low beta but no detected supernatants cells, kept FCS-free conditions FCS-containing medium. Moreover, IL-6 mRNA was also present 45 55% cultured presence FCS as visualized by situ hybridization, whereas remained undetectable. After prestimulation with LPS alpha,...

EBV-induced gene 3 (EBI3) can associate with p28 to form the heterodimeric cytokine IL-27, or p35 subunit of IL-12 EBI3/p35 heterodimer, recently named IL-35. In mice, IL-35 has been shown be constitutively expressed by CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg cells) and suggested contribute their suppressive activity. this study, we investigated whether human Treg express Double-staining analysis thymuses showed that neither Foxp3(+) nor CD25(+) coexpressed EBI3. Similarly, present in...

Abstract Interleukin (IL)‐27 is a newly described member of the IL‐12 family. It heterodimeric cytokine composed two subunits, p28 and Epstein–Barr virus‐induced gene 3 (EBI3). In vitro studies have shown that IL‐27 mainly produced by activated monocytes dendritic cells. induces proliferation naïve CD4‐positive T cells synergizes with for interferon‐γ (IFN‐γ) production. Knock‐out mice receptor (WSX‐1/TCCR) impaired Th1 responses form abnormal granulomas when injected bacillus...

CD1d-reactive invariant NKT (iNKT) cells have been implicated in a number of experimental models human pathologies. Given the scope their immunoregulatory activities mediated through distinct cytokine patterns, it has proposed that this functional diversity originates from iNKT subpopulations. In study, we report CD161(+) are intrinsically endowed with capacity to generate IL-17, but require TGF-β, IL-1β, and IL-23 carry out potential. IL-17-producing already present cord blood but, contrast...

Abstract IL-27 is a novel heterodimeric cytokine of the IL-12 family that plays an important role in regulation T cell responses. Its on human B cells has not been previously studied. In this study, we show both chains receptor complex, IL-27R and gp130, are constitutively expressed at surface naive memory tonsillar cells, induced germinal center following CD40 stimulation. strong STAT1 STAT3 phosphorylation, whereas it moderate low activation cells. T-bet expression stimulated by or Ig...

Type I IFNs, IFN-alpha and IFN-beta, are early effectors of innate immune responses against microbes that can also regulate subsequent adaptive immunity by promoting antimicrobial Th1-type responses. In contrast, the ability IFN-beta to inhibit autoimmune Th1 is thought account for some beneficial effects therapy in treatment relapsing remitting multiple sclerosis. To understand basis paradoxical on expression responses, we developed an vitro model monocyte-derived dendritic cell...

Abstract Epstein–Barr virus (EBV)‐associated Hodgkin lymphoma (HL) and nasopharyngeal carcinoma (NPC) usually occur in patients without clinically manifest deficiencies anti‐viral immunity. In spite of expressing viral proteins, both tumours are apparently able to escape EBV‐specific immunity vivo . EBI3 is an EBV‐induced cytokine homologous the interleukin (IL)‐12 p40 subunit can heterodimerize with IL‐12 p35. It has been suggested that may function antagonize inhibit development a Th1...

Invariant NKT (iNKT) cells constitute a versatile T cell subset with important regulatory functions, which are thought to result essentially from their capacity promptly produce cytokines that influence the Th1/Th2 balance. In this study, we report these can also express Foxp3, an transcriptional regulator associated suppressive activity, once they have been exposed TGF-β. Foxp3 was expressed by iNKT both peripheral and cord blood. CD4(+) acquired expression preferentially, although lower...

Nonhuman primates are naturally infected with a B-lymphotropic herpesvirus closely related to Epstein-Barr virus (EBV). These simian EBV share considerable genetic, biologic, and epidemiologic features human EBV, including virus-induced tumorigenesis. However, latent, transformation-associated viral genes demonstrate marked sequence divergence among species despite the conserved functions. We have cloned latent membrane protein 1 (LMP1) homologs from infecting baboons (cercopithicine 12,...

Multiple sclerosis (MS) is an autoimmune disorder characterized by chronic inflammation, demyelination, and neuronal damage. During autoimmunity, cytokines are important mediators of the inflammation. In this line, interleukin-27 (IL-27) modulates inflammation can be produced directly at inflammatory sites such as in joints during rheumatoid arthritis or central nervous system (CNS) MS. While animal models MS, treatment with IL-27 decreases disease severity, its role humans not clearly...

Significance Interleukins are small secreted proteins that drive immune cell communication. Understanding how cells produce interleukins is thus key for decoding and modulating responses. Our study elucidates the molecular mechanisms of interleukin 27 (IL-27) biosynthesis, a cytokine in control autoimmunity infections. IL-27 composed two subunits, α β. In humans, these have to assemble form bioactive IL-27, whereas mice, IL-27α can be alone, reactions reducing sepsis-related mortality....