Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The majority of CLLs are of B lineage derivation with about 5 per cent of cases of T lineage. Although morphologically resembling the small peripheral blood B cell, by virtue of the expression of B cell restricted and associated cell surface antigens, B-CLLs are not the neoplastic counterparts of normal resting B cells. Similar to the peripheral blood B cell, B-CLLs express CD19, CD20, CD21, CD24, CD40, CD44, CD45R, and sIgM/D. However, unlike peripheral blood B cells, B-CLLs generally do not express C3b complement receptor, LFA-1, or CD22. In addition, B-CLLs express the T cell associated antigen CD5, and a number of antigens induced on normal B cells following in vitro activation (B5, Blast-1, CD23). These findings support the hypothesis that B-CLLs are the neoplastic counterparts of one or more unique subpopulations of normal B cells. Normal CD5+ B cells, which phenotypically resemble B-CLL, are present in fetal lymphoid tissues and in small numbers in adults. Moreover, normal CD5+ B cells are present in increased numbers in patients with autoimmune diseases and a subset of normal in vitro activated B cells phenotypically resemble B-CLL. Similar studies into the state of differentiation of T-CLL cells suggest that although most cases resemble normal activated T helper cells, a significant number are the neoplastic counterparts of natural killer cells. Recent studies have examined the function of B and T cells in B-CLL. Although controversial, these studies suggest that the in vitro response to mitogens and cytokines of B-CLL cells is abnormal. T cell proliferation in B-CLL is depressed due to an inability to produce sufficient T cell growth factor (IL-2) as well as a poor response to exogenous IL-2 possibly from ineffective IL-2 receptor expression. Purified populations of T helper and T suppressor cells demonstrate insufficient support of Ig production by normal B cells as well as excess suppression, respectively. These studies have further supported the previous hypothesis that the depressed cellular and humoral immunity in CLL is multifactorial with both abnormal B and T cell function.
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PMID:Immunobiology of chronic lymphocytic leukemia. 218 99

The ileal Peyer's patch (PP) plays a central role in B cell development in young sheep and it is hypothesized that this B cell development occurs independent of extrinsic antigen and T cells. Therefore, it was of interest to examine ileal PP follicular (iPf) B cell responses to CD40 ligand, a molecule integral to T cell-dependent B cell development. A variable level of CD40 expression was detected on a subpopulation of iPfB cells and J558L cells, expressing a membrane form of mouse CD40 ligand (mCD40L), interacted specifically with the CD40 molecule on iPfB cells. In response to mCD40L the non-S phase iPfB cells were rescued from apoptotic cell death and there was a marked proliferative response but viable cell number remained relatively constant. The mCD40L also induced decreased cytoplasmic cAMP levels, blocked anti-Ig-induced iPfB cell death and induced functional IL-2 receptor expression on a subpopulation of iPfB cells. Many of the mCD40L-induced responses of iPfB cells were similar to those reported for germinal centre and immature B cells, and indicated that cognate T cell-B cell interaction could influence iPfB cell proliferation and differentiation. Finally, that mCD40L induced iPfB cell activation and differentiation was evident as increased expression of CD5, the BAQ44A molecule, the CACT65A molecule and the expansion of surface IgG1+ B cells. These mCD40L-induced phenotypic changes were also observed on subpopulations of freshly isolated iPfB cells and jejunal PP follicular B cells. However, few iPfB cells had a phenotype similar to that observed in co-culture with mCD40L and this suggested that T cell-dependent B cell development may play a minor role in ileal PP B cell development. The possible significance of CD40 signalling is discussed in terms of the selection of iPfB cells during development.
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PMID:CD40 signalling in ileal Peyer's patch B cells: implications for T cell-dependent antigen selection. 754 Aug 60

In this report, the effect of ligation of a number of B-cell surface molecules upon expression of CD25, the 55-kDa inducible component of the IL-2 receptor complex found on T and B lymphocytes, is reported. IL-4 is the only cytokine apparently capable of promoting CD25 expression in human high-density quiescent tonsillar B cells; neither IL-10 nor IL-13 could induce CD25 expression. Cross-linking of the antigen receptors or CD40 with antibody elicited CD25 expression in a dose-dependent manner. Stimulation with anti-CD40 promoted CD25 expression in approximately 25% of B cells, while anti-Ig caused 80% or more of cells to become CD25+. In experiments where the stimuli were used in combination, some additive effects upon CD25 expression were noted, but no obvious synergistic effects could be detected.
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PMID:Anti-immunoglobulin and anti-CD40 stimulation induces CD25 expression by resting human tonsillar B lymphocytes. 754 28

Protein tyrosine phosphorylation is known to play key roles in lymphocyte signal transduction, and phosphotyrosine phosphatases (PTP) can act as both positive and negative regulators of these lymphocyte signals. We sought to examine the role of PTP further in these processes by characterizing the effects of bis(maltolato)-oxovanadium(IV) (BMLOV), previously known to be a nontoxic insulin mimetic agent in vivo. BMLOV was found to be a potent phosphotyrosine phosphatase inhibitor. BMLOV induced cellular tyrosine phosphorylation in B cells in a pattern similar to that observed following antigen receptor stimulation, whereas little tyrosine phosphorylation was induced in T cells. In B cells, BMLOV treatment resulted in tyrosine phosphorylation of Syk and phospholipase C gamma 2, while sIgM-induced signals were inhibited. By contrast, T cell receptor signals were moderately increased by BMLOV, and the cells displayed greater induction of IL-2 receptor without toxicity. The compound selectively induced apoptosis in B cell lymphoma and myeloid leukemia cell lines, but not in T cell leukemia or colon carcinoma cells. Interleukin-4 plus anti-CD40 antibody treatment of normal human peripheral B cells rescued the cells from BMLOV-induced death. These results suggest that phosphotyrosine phosphatase inhibitors can activate B cell signal pathways in a lineage-specific manner, resulting in desensitization of receptor-mediated signaling and induction of apoptosis.
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PMID:Lineage-specific induction of B cell apoptosis and altered signal transduction by the phosphotyrosine phosphatase inhibitor bis(maltolato)oxovanadium(IV). 765 67

To study the role of interleukin (IL)-6 as a growth and differentiation factor for Epstein-Barr virus (EBV)-transformed B lymphocytes, we transfected the cDNA coding for human IL-6 in a monoclonal IgG1-secreting EBV B cell line. Two independent clones were selected that constitutively secreted high amounts of IL-6. These clones showed enhanced levels of IL-6 and tumor necrosis factor alpha secretion when compared to non-IL-6 transfected controls. Moreover, they could efficiently be recovered from low cell density cultures in limiting dilutions when plated on a feeder layer of heterologous EBV B cells. IL-6-induced phenotypical changes comprised a significant rise in immunoglobulin secretion levels and enhanced membrane expression of CD25 (the beta chain of the IL-2 receptor) and of the B cell differentiation antigen CD40. IL-6-dependent down modulation of CD38 and of the adhesion structure VLA4 were also observed. Our data support the notion that IL-6 can serve as an growth and differentiation factor for EBV B cells.
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PMID:Expression of the IL-6 gene induces differentiation of a human monoclonal EBV-transformed B cell line. 839 33

c-Rel is a lymphoid-specific member of the NF-kappaB/Rel family of transcriptional factors. To investigate the role of c-Rel in B lymphocyte function, we generated a c-Rel(-/-) mouse via a gene targeting approach. Although early lymphocyte development is normal in c-Rel(-/-) mice, there are significantly fewer B cells displaying a memory (IgM/IgD-) phenotype. Upon immunization, c-Rel(-/-) mice generate fewer B cells with a germinal center (PNAhi) phenotype. In vitro, c-Rel(-/-) B cells proliferate poorly upon ligation of their surface IgM or CD40 receptors or when stimulated with either lipopolysaccharide (LPS) or T cell help. Early molecular events that precede proliferation, such as increases in RNA synthesis as well as IL-2 receptor alpha chain expression, are greatly diminished in c-Rel(-/-) B cells. Furthermore, c-Rel(-/-) B cells are impaired in the ability to receive survival signals generated by anti-IgM or LPS. In contrast, CD40-mediated cell survival is normal in c-Rel(-/-) B cells, suggesting the involvement of a survival-signaling pathway that is independent of c-Rel. When c-Rel (-/-) B cells are co-stimulated with either anti-IgM and CD40 or LPS and CD40, they are rendered capable of progressing through the cell cycle. Finally, co-culture experiments suggest that the defects observed in c-Rel(-/-) B cells are intrinsic to the cell and can not be rescued through either cell-cell contact or addition of soluble factors. Thus, c-Rel is requisite for differentiation to the germinal center and memory B cells in vivo and is required for the transduction of survival and cell cycle progression signals mediated by anti-IgM and LPS in vitro. Furthermore, while c-Rel is involved in CD40-induced proliferation, it is apparently dispensable for the survival signals transduced by CD40.
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PMID:c-Rel is essential for B lymphocyte survival and cell cycle progression. 986 67

Epstein-Barr virus is associated with several human malignancies including Burkitt's lymphoma, nasopharyngeal carcinoma, and Hodgkin's disease (HD). To examine the effect of Epstein-Barr virus nuclear antigen 1 (EBNA-1) in the pathogenesis of HD, we transfected the gene into the HD cell line L428. EBNA-1 expression was associated with significantly enhanced CD25 expression (interleukin 2 [IL-2]-receptor alpha chain) in transient and stably transfected L428 cells but did not affect the expression of IL-2 receptor beta and gamma chains. There was no up-regulation of the B-cell activation molecules CD23, CD30, CD39, CD40, CD44, CD71, and CD54 (intercellular adhesion molecule 1) or enhanced production of IL-6, IL-10, lymphotoxin alpha, and the soluble form of CD25. Stable EBNA-1-expressing L428 cells were nontumorigenic in SCID mice but showed enhanced lymphoma development in nonobese diabetic-SCID mice compared to mock-transfected cells.
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PMID:Expression of epstein-barr virus nuclear antigen 1 is associated with enhanced expression of CD25 in the Hodgkin cell line L428. 988 70

We have recently shown that expression of the enzyme indoleamine 2, 3-dioxygenase (IDO) during murine pregnancy is required to prevent rejection of the allogeneic fetus by maternal T cells. In addition to their role in pregnancy, IDO-expressing cells are widely distributed in primary and secondary lymphoid organs. Here we show that monocytes that have differentiated under the influence of macrophage colony-stimulating factor acquire the ability to suppress T cell proliferation in vitro via rapid and selective degradation of tryptophan by IDO. IDO was induced in macrophages by a synergistic combination of the T cell-derived signals IFN-gamma and CD40-ligand. Inhibition of IDO with the 1-methyl analogue of tryptophan prevented macrophage-mediated suppression. Purified T cells activated under tryptophan-deficient conditions were able to synthesize protein, enter the cell cycle, and progress normally through the initial stages of G1, including upregulation of IL-2 receptor and synthesis of IL-2. However, in the absence of tryptophan, cell cycle progression halted at a mid-G1 arrest point. Restoration of tryptophan to arrested cells was not sufficient to allow further cell cycle progression nor was costimulation via CD28. T cells could exit the arrested state only if a second round of T cell receptor signaling was provided in the presence of tryptophan. These data reveal a novel mechanism by which antigen-presenting cells can regulate T cell activation via tryptophan catabolism. We speculate that expression of IDO by certain antigen presenting cells in vivo allows them to suppress unwanted T cell responses.
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PMID:Inhibition of T cell proliferation by macrophage tryptophan catabolism. 1022 76

Bacterial genomic DNA, plasmid DNA (pDNA) and synthetic oligodeoxynucleotides (ODN) containing immunostimulatory DNA sequences (ISS) have been proposed to foster a Th1 response via the release of type 1 cytokines from macrophages, dendritic cells, NK cells and B cells. In this study, we show that ISS-enriched DNA up-regulates a distinct profile of cell surface molecules on macrophages and B cells in vitro and in vivo. ISS-ODN and ISS-containing pDNA enhanced the expression of antigen presentation molecules (MHC class I and II), co-stimulatory molecules (B7-1, B7-2 and CD40), cytokine receptors (IFN-gamma receptor and IL-2 receptor), an adhesion molecule (ICAM-1) and an Fc receptor (Fcgamma receptor) on murine B cells or bone marrow-derived macrophages. The increased expression of these surface molecules is seen in purified cell populations and is largely independent of the effects of type 1 cytokines. Splenic antigen-presenting cells stimulated with ISS-ODN in vivo efficiently activate naive T cells and bias their differentiation toward a Th1 phenotype in vitro. Thus, the induction of both type 1 cytokines and a distinct profile of cell surface molecules contributes to the potent immunostimulatory effects of ISS-containing DNA on innate and adaptive immunity.
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PMID:Enhancement of antigen-presenting cell surface molecules involved in cognate interactions by immunostimulatory DNA sequences. 1038 44

CD40 signaling induces B cell proliferative and differentiation responses that can be modulated by many different cytokines. Cytokines in the IL-2 receptor gamma chain (gammac)-common family are known to play an integral role in B cell development. Therefore, we investigated the possibility that CD40 signaling induced B cell responsiveness to multiple gammac-common cytokines and that individual gammac-common cytokines induced distinct B cell responses. B cells were isolated from lymphoid follicles of sheep Peyer's patches (PP) and co-cultured with murine CD40 ligand (mCD40L). CD40 signaling induced PP B cell responsiveness to recombinant human IL-2, IL-4, IL-7 and IL-15. mCD40L-induced B cell growth was enhanced by combining IL-4 with a second gammac-common cytokine and sustained B cell growth required co-stimulation with IL-4 plus IL-2, IL-7 and IL-15. gammac-common cytokine responsiveness remained dependent upon CD40 signaling, and removal of mCD40L resulted in B cell differentiation and cell death. Similar proliferative responses to mCD40L and gammac-common cytokines were observed for both immature (ileal) and mature (jejunal) PP B cells. Finally, the capacity of CD40-activated B cells to respond to multiple gammac-common cytokines was analyzed with individual PP B cell clones. All B cell clones displayed similar proliferative responses to IL-2 but quantitatively different responses to IL-4, IL-7 and IL-15. The biological significance of B cell responsiveness to multiple gammac-common cytokines is discussed.
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PMID:CD40 signaling induces B cell responsiveness to multiple members of the gamma chain-common cytokine family. 1038 47


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