Abstract:
:The cytokines interleukin (IL)-6, IL-11, ciliary neurotrophic factor (CNTF), leukemia inhibitor factor (LIF), oncostatin M (OSM) and probably the recently cloned cytokine cardiotrophin-1, signal, in combination with their specific receptors, through the common signal transducer gp130. Here, we report that the signaling activities of IL-6, IL-11, CNTF and OSM/LIF can be specifically blocked by different anti-gp130 monoclonal antibodies (mAb). Furthermore, we found two mAb, B-P8 and B-S12, which directly activate gp130 independently of the presence of cytokines or their receptors. This agonistic activity includes induction of cytokine-dependent cell proliferation and stimulation of acute-phase protein synthesis in liver cells. Compared to B-P8 mAb, the B-S12 mAb exhibited the strongest agonistic activity, while both mAb are synergistic in their action. This activity could not be blocked by inhibiting mAb against IL-6 and the IL-6 receptor. In contrast to F(ab')2 of B-S12 which still could activate gp130, Fab fragments completely lost their agonistic activity. Activation by tyrosine phosphorylation of the transcription factors Stat1 and APRF/Stat3 was also induced by B-S12 and B-P8, suggesting that both mAb induce homodimerization of gp130. Since hematopoietic stem cells express gp130 on their plasma membrane, it was anticipated that the agonistic anti-gp130 mAb could stimulate the proliferation of these stem cells. Indeed, B-S12 and B-P8 were able to stimulate CD34+ cells. In summary, our data show for the first time that mAb against gp130 can specifically block the action of distinct IL-6-type cytokines that signal through gp130. Such mAb might be of great value for therapeutic applications in diseases where a single cytokine action needs to be inhibited. In addition, the agonistic gp130 mAb may be used as growth factors for maintenance and expansion of stem cells prior to grafting.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Wijdenes J,Heinrich PC,Müller-Newen G,Roche C,Gu ZJ,Clément C,Klein Bdoi
10.1002/eji.1830251240subject
Has Abstractpub_date
1995-12-01 00:00:00pages
3474-81issue
12eissn
0014-2980issn
1521-4141journal_volume
25pub_type
杂志文章abstract::Rabbit antibodies to Atlantic cod (Gadus morhua L.) immunoglobulin were affinity purified and used to screen cDNA libraries from spleen and head kidney mRNA. cDNA clones for both the secretory and membrane-bound heavy (H) chain were isolated, the nucleotide and deduced amino acid sequences of which are reported here. ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830211219
更新日期:1991-12-01 00:00:00
abstract::An immunoglobulin epsilon-chain fragment was synthesized in E. coli by cloning and expression of the gene coding for the second, third and fourth constant domains of the human IgE heavy chain. The bacterial CH2-4 polypeptide product was assembled by oxidation into a covalently linked dimeric epsilon-chain molecule pre...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830150920
更新日期:1985-09-01 00:00:00
abstract::Somatic hypermutation in B cells undergoing T cell dependent immune responses generates high affinity antibodies that provide protective immunity. B cells also switch from the expression of immunoglobulin (Ig) M and IgD to that of other Ig classes through somatic DNA recombination. Recent work has implicated DNA stran...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/1521-4141(200202)32:2<316::AID-IMMU316>3.0
更新日期:2002-02-01 00:00:00
abstract::The role of monocytes, B cells, and adherent and nonadherent T cells in the response of purified protein derivative of tuberculin (PPD) as measured by [3H]thymidine uptake in vitro has been explored. The response to PPD was found to be highly dependent on monocytes, to approximately the same extent as previously found...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830090411
更新日期:1979-04-01 00:00:00
abstract::Plasma cells secreting IgG, M, and A abound in the synovium of patients with rheumatoid arthritis, yet their immunoglobulin repertoire and clonal relationship remain to be elucidated. Locally synthesized immunoglobulins probably contribute to the chronic joint inflammatory processes which are characteristic of these p...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830270219
更新日期:1997-02-01 00:00:00
abstract::Naturally occurring CD4+CD25(high) regulatory T cells (nTreg) are essential for maintaining tolerance. FOXP3 has been established as a molecular marker of nTreg; however, FOXP3 cannot be used as a reliable marker for bona fide human nTreg since effector T cells also up-regulate FOXP3 expression upon activation. Despit...
journal_title:European journal of immunology
pub_type: 评论,杂志文章
doi:10.1002/eji.200940117
更新日期:2009-12-01 00:00:00
abstract::Alpha4-mediated signaling is involved in a variety of functions in mammalian cells. To determine whether this is true for immunocompetent cells, we generated mutant (Lck-alpha4-) mice in which the alpha4 gene was deleted in a T cell-specific manner using the Cre/loxP system. These mice showed impaired early T cell dev...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200323720
更新日期:2003-07-01 00:00:00
abstract::All leukocytes express the cell surface glycoprotein CD45, which has intrinsic intracellular protein tyrosine phosphatase activity. CD45 is known to play a regulatory role in activation-induced signaling in lymphocytes; however, little is known of its role in non-lymphoid leukocytes. Therefore, we examined the potenti...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/(SICI)1521-4141(199905)29:05<1467::AID-IMM
更新日期:1999-05-01 00:00:00
abstract::Single-positive thymocytes are the immediate precursors of peripheral recent thymic emigrants (RTE) which develop into mature peripheral T cells. The functional ability of RTE is unclear but their state of differentiation may be relevant to the development of tolerance to peripheral "self" antigens. Since RTE are diff...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830240738
更新日期:1994-07-01 00:00:00
abstract::Co-culture of purified T and B cells obtained from cytochrome c-specific TCR- and hen egg lysozyme (HEL)-specific Ig-transgenic mice was used to examine the role of B cell receptor (BCR) ligation and TCR affinity on the efficiency of T-B cell collaboration. The results showed that BCR ligation of naive B cells with HE...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/(SICI)1521-4141(199812)28:12<4037::AID-IMM
更新日期:1998-12-01 00:00:00
abstract::A method is described for radiolabeling polyanionic macromolecules by the formation of an electrostatic complex with a radioiodinated tyramine conjugated DEAE-dextran. Data is presented on the use of this technique for the detection and quantitation of immunospecific binding of polynitrophenylated proteins, deoxyribon...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830050604
更新日期:1976-06-01 00:00:00
abstract::Here we demonstrate that components of the entire complement cascade are fixed on the surface of erythrocytes infected with the human malarial parasite Plasmodium falciparum. Despite the activation of lytic complement factors, no complement-mediated lysis of P. falciparum-infected erythrocytes occurred only in the abs...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830271034
更新日期:1997-10-01 00:00:00
abstract::The present report describes functional characteristics of a monoclonal antibody (mAb), TA/211, which is reactive with a common determinant of the human CD45 molecules. When added to purified testing human T cells, TA/211, which is itself not mitogenic, leads to a strong proliferative response in combination with subm...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830190226
更新日期:1989-02-01 00:00:00
abstract::T lymphocytes can be activated and induced to proliferate through stimulation of the CD2 glycoprotein with functional combinations of CD2 antibodies. However, this mechanism of signal transduction via CD2 is still not fully understood. We have investigated which molecules on the T cell surface preferentially associate...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/1521-4141(200205)32:5<1509::AID-IMMU1509>3
更新日期:2002-05-01 00:00:00
abstract::Membrane-coated microvesicles (MVs) have been identified as important mediators in intercellular communication. During the process of apoptosis, dying cells dynamically release MVs. Neutrophils are the most abundant type of leukocytes in the circulation. Due to their very short lifespan, it is likely that they are the...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201546203
更新日期:2017-05-01 00:00:00
abstract::Fas is a cell surface molecule that is expressed on a wide array of cell types and triggers apoptosis. While in most situations Fas ligation activates programmed cell death, on resting T lymphocytes it can co-stimulate proliferation with the T cell receptor (TCR)/CD3 complex. This incongruity suggests that Fas may eli...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830260505
更新日期:1996-05-01 00:00:00
abstract::Endogenous superantigens (SAg) presented by MHC class II IA molecules induce slow-evolving negative selection of alpha beta T cells. The role of both B and gamma delta T cells on the regulation of these SAg-specific alpha beta T cell responses was addressed in IA(b+)IE(b-) C57BL/6 mice bearing genetically induced B ce...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/1521-4141(200109)31:9<2811::aid-immu2811>3
更新日期:2001-09-01 00:00:00
abstract::A murine monoclonal IgM antibody recognizes an antigen (Mo3e) found on the surface of human peripheral blood monocytes stimulated with phorbol 12-myristate 13-acetate (PMA), lipopolysaccharide and muramyl dipeptide and blocks the monocyte response to migration inhibitory factor (MIF). We utilized Western blot and immu...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830190423
更新日期:1989-04-01 00:00:00
abstract::Spleen cells from BALB/c mice were fused with the nonsecreting myeloma line X63.Ag8.6.5.3 seven days after immunization with NP-CG (4-hydroxy-3-nitrophenyl) acetyl-chicken gamma-globulin. The hybrid cell lines obtained were analyzed for heavy and light chain distribution, fine specificity, and idiotype. The majority o...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830111109
更新日期:1981-11-01 00:00:00
abstract::The monoclonal antibody W6/32.1 recognizes a public determinant on the HLA-A, B and C antigens of all tested human haplotypes. Though the antibody does not bind to normal mouse cells of any H-2 haplotype, it does show an unexpected specificity for the T cell leukemia line MBL-2 from a C57BL/6 mouse. It is shown that t...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830130213
更新日期:1983-02-01 00:00:00
abstract::The T cell-dependent differentiation and function of B lymphocytes are tightly regulated by TNF ligands (L) and receptors interactions, such as CD40/CD40L, CD27/CD70 and CD134/CD314L. The LIGHT/HVEM system [homologous to lymphotoxin, inducible expression, competing for GpD of herpes virus, that binds to the herpes vir...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200425598
更新日期:2004-12-01 00:00:00
abstract::IFN-gamma produced by CD4+ T helper 1 (Th1) cells promotes protection against intracellular pathogens. Antigen activation of Th1 cells is an important mode of IFN-gamma induction, but here we analyze a second, antigen-nonspecific pathway capable of inducing full IFN-gamma transcription. IL-12 or IL-18 alone do not ind...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/(SICI)1521-4141(199902)29:02<548::AID-IMMU
更新日期:1999-02-01 00:00:00
abstract::This study describes a general strategy to produce hybrid monoclonal antibodies that are capable of targeting human cytotoxic T lymphocytes (CTL) against any cell carrying the appropriate target antigen. This is done by fusing a HAT-sensitive, G418-resistant anti-T3 hybridoma with immune spleen cells (or with other hy...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830170118
更新日期:1987-01-01 00:00:00
abstract::The lectin leucoagglutinin has been used to induce reactivity to interleukin 2 (IL2) in unseparated spleen cells and in highly purified Lyt-2+ lymph node T cells. Recombinant human IL2 and various other IL2-containing preparations, including concanavalin A-induced spleen cell supernatant, were compared for their capac...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830150405
更新日期:1985-04-01 00:00:00
abstract::In the present study, interleukin 1 (IL 1)-containing media from different sources, namely a murine macrophage cell line (P388D1), rabbit peritoneal macrophages, and human peripheral blood mononuclear cells, were compared for their effect on thymocyte proliferation and on collagenase and PGE2 secretion by chondrocytes...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830140603
更新日期:1984-06-01 00:00:00
abstract::It was previously observed that MOPC-315EL, a subline of the BALB/c myeloma tumor MOPC-315, varies in its ability to interact with primary anti-H-2d cytotoxic thymus-derived lymphocytes (CTL) while remaining invariant in its expression of cell surface antigens recognized by anti-H-2d sera. This paper demonstrates (a) ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830080907
更新日期:1978-09-01 00:00:00
abstract::Cathelicidins are a family of host defence peptides that are known to selectively alter innate immunity in response to infection and other changes in immune status. A study in this issue of the European Journal of Immunology elucidates a new role for mouse cathelin-related antimicrobial peptide in the adaptive immune ...
journal_title:European journal of immunology
pub_type: 评论,杂志文章
doi:10.1002/eji.201142055
更新日期:2011-10-01 00:00:00
abstract::To elucidate the mechanism of autoimmune disease in neonatally thymectomized (NTX) mice, we have investigated the responsiveness of the self-reactive T cells which have not undergone clonal deletion in such animals. Consistent with a recent report (Yuuki et al., Eur. J. Immunol. 1990. 20: 1475), T cells bearing V beta...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830210310
更新日期:1991-03-01 00:00:00
abstract::Splenic T cells were primed, after removal of alloreactive cells, to beef insulin on allogeneic antigen-presenting cells (APC). The fine specificity of in vitro secondary response was tested in combinations H-2b (responder) T cell-H-2k (nonresponder) APC, and vice versa, using separated chains of beef and pork insulin...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830130810
更新日期:1983-08-01 00:00:00
abstract::An antigen-specific T-T hybridoma was mutagenized with ethylmethane sulfonate and negatively selected by anti-Ly-6 antibody-induced growth inhibition. One of the mutants generated, M4/8, had lost surface expression of a T cell receptor (TcR) V beta 8 epitope detected on the surface of the parental cell line. However, ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830200702
更新日期:1990-07-01 00:00:00