bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of IgG production by suppressor FcγRII+ T hybridomas
Authors: Brunati Silvana , Moncuit Janine , Fridman Wolf H. , Teillaud Jean‐Luc 
Published: March 2007

AbstractIn this work, we analyzed the immunoglobulin heavy (H) and light (L) chain production by two variant B hybridomas, UN2.C3 and UN2.C17.K1 co‐cultured with cells from a FcγRII, IgG‐binding factor (IgG‐BF)‐producer T hybridoma (T2D4.C1) or with cells of a FcγRII−, IgG‐BF‐nonproducer variant (D10C5). We showed that only the FcγRII hybridoma directly inhibits the IgG secretion by UN2.C3 through a soluble mediator. This inhibition affects the H and L chain synthesis as well as the H and L chain‐encoding mRNA steady state. No apparent cytotoxic effect could be detected. In contrast, the production of ϰ chain by an H chain‐negative variant (UN2.C17.K1) was unaffected. This indicates that a complete IgG molecule is required to observe the inhibitory effect induced by T2D4.C1. The pattern of effector/target cell interactions observed in our work suggests that the soluble factor involved in the suppression of IgG production is IgG‐BF, able to transiently modify the IgG gene expression in target cells.
T cell receptor‐negative thymocytes from SCID mice can be induced to enter the CD4/CD8 differentiation pathway
Authors: Shores Elizabeth W. , Sharrow Susan O. , Uppenkamp Ingeborg , Singer Alfred 
Published: March 2007

AbstractIn order to investigate the role of T cell receptor (TcR) expression in thymocyte maturation, we have analyzed thymocytes from C.B‐17/SCID mice, which are unable to productively rearrange their antigen receptor genes and fail to express TcR. Despite this defect, SCID thymocytes are functional as they produce lymphokines and proliferate in response to a variety of stimuli. Phenotypic analysis revealed that thymocyte populations from young adult SCID mice resemble thymocyte populations from normal embryonic mice in that they are large, Thy‐1.2+, CD4−, CD8−, TcR− and enriched in CD5lo, IL2R+ and Pgp1+ cells. However, other TcR− populations normally present in adult mice (i.e., CD4−CD8+ cells and CD4+CD8+ cells) are absent from the thymus of TcR− adult SCID mice. To understand the basis of the developmental arrest of TcR− SCID thymocytes at the CD4−CD8− stage of differentiation, we analyzed thymi from the occasional “leaky” SCID mouse which possesses small numbers of TcR+ thymocytes. We found that the presence of TcR+ cells within a SCID thymus was invariably associated with the presence of CD4+ and/or CD8+ SCID thymocytes. Interestingly, however, the CD4+/CD8+ SCID thymocytes were not themselves necessarily TcR+. That is, emergence of SCID thymocytes expressing CD4/CD8 was tightly linked to the presence of TcR cells within that SCID thymus, but the SCID thymocytes that expressed CD4/CD8 were not necessarily the same cells that expressed TcR. Finally, we found that the introduction into TcR− SCID mice of normal bone marrow cells that give rise to TcR+ cells within the SCID thymus promoted the differentiation of SCID thymocytes into CD4−CD8+ and CD4+CD8+ TcR− cells.These data indicate that TcR+ cells within the thymic milieu provide critical signals which promote entry of CD4−CD8−TcR− precursor T cells into the CD4/CD8 differentiation pathway. When applied to differentiation of normal thymocytes, these findings may imply a critical role for early appearing CD4−CD8− TcR (γ/δ)+ cells in initiating normal thymic ontogeny.
Antigen density on target cells determines the immunosuppressive potential of rat IgG2b monoclonal antibodies
Authors: Kummer Udo , Thierfelder Stefan , Mysliwietz Josef 
Published: March 2007

AbstractThe current studies were designed to determine the relevance of T cell antigen density, besides antibody isotype, with regard to the success of antibody serotherapy. We compared the immunosuppressive effects of two rat IgG2b monoclonal anti‐Thy‐1 antibodies, RmT1 and 30‐H12, with distinct binding sites in a graft‐vs.‐host disease (GVHD) model of fully H‐2 and I‐A regionmismatched bone marrow transplantation, making use of the difference in Thy‐1.2 antigen density between homozygous (BALB/c) and heterozygous (BALB/c×AKR/J)F1 GVHD‐promoting donor cells. Antibodies RmT1 (directed against a monomorphic determinant on mouse Thy‐1) and 30‐H12 (reactive with the Thy‐1.2 allele‐specific determinant) did not differ in their anti‐GVHD activity with regard to Thy‐1.2 homozygous grafts. However, in the region of a critical number of binding sites a small difference in the amounts of the two antibodies bound (about 8×103 IgG molecules/cell) obviously accounts for a great difference in anti‐GVHD activity. This is shown in a two haplotype host‐graft disparity between C57BL/6 recipients treated with either RmT1 or 30‐H12 before challenging them with (BALB/c×AKR/J)F1 grafts, where the Thy‐1.2 antigen concentration is approximately 50% compared to the density on BALB/c lymphocytes. Here, mAb 30‐H12 loses its remarkable in vivo immunosuppressive quality, whereas RmT1 treatment protects mice against lethal GVHD. Binding sites were quantitated using a computerized approach for the analysis of data from ligand binding experiments of the respective mAb, RmT1 and 30‐H12, coated to LN cells of BALB/c and F1 hybrid origin. Furthermore, the in vivo immunosuppressive activity of rat IgG2b antibodies directed against Thy‐1 was found to correlate with their ability to generate stable antibody‐Clq complexes on the cell surface of immunocompetent T cells.
Inhibition of human interleukin 4‐induced IgE synthesis by a subset of anti‐CD23/FcϵRII monoclonal antibodies
Authors: Bonnefoy Jean‐Yves , Shields John , Mermod Jean‐Jacques 
Published: March 2007

AbstractSpecific monoclonal antibodies (mAb) directed against the CD23 antigen were used to study human interleukin 4 (hIL 4)‐induced IgE production by blood and tonsillar mononuclear cells. Both peripheral blood and tonsillar mononuclear cells stimulated by hIL 4 expressed membrane CD23 as detected by the binding of all anti‐CD23 mAb. Nevertheless, two sets of anti‐CD23 mAb could be distinguished. The first set, including mAb25, was able to decrease significantly hIL 4‐induced IgE synthesis by mononuclear cells. The second set, including EBVCS#1, did not affect hIL 4‐induced IgE synthesis. All the anti‐CD23 mAb were able to bind specifically to a human B cell line expressing recombinant CD23. Inhibition experiments revealed that the two sets of anti‐CD23 mAb did not recognize the same epitope on the CD23 antigen. In fact, all the anti‐CD23 mAb, except EBVCS#1, were able to inhibit IgE binding to CD23 on RPMI 8866 cells. Moreover, the first set of antibodies, which decreased IgE production, was able to up‐regulate membrane CD23 expression on hIL4‐stimulated tonsillar mononuclear cells. Conversely, EBVCS#1, which had no effect on IgE production, did not affect hIL 4‐induced CD23 expression. These results indicate that CD23 plays a key role in human IgE synthesis.
Chemical residues of ganglioside molecules involved in interactions with lymphocyte surface targets leading to CD4 masking and inhibition of mitogenic proliferation
Authors: Grassi Fabio , Lopalco Lucia , Lanza Paola , Ciccomascolo Franca , Cazzola Flavia , Martino Alessandro Di , Kirschner Gunther , Callegaro Lanfranco , Chieco‐Bianchi Luigi , Siccardi Antonio G. 
Published: March 2007

AbstractHuman lymphocyte CD4 becomes undetectable in the presence of exogenous gangliosides (CD4 masking), as originally described by Offner et al. (J. Immunol. 1987. 139: 3295). CD4 masking is apparently due to in situ rearrangement of the glycoprotein; since no direct binding of ganglioside to CD4 could be demonstrated, it was suggested that the effect could be mediated by interactions with other, as yet unidentified, surface structures. To gain insight into the structural requirements of the interaction(s) that leads to CD4 masking, we assayed the effects of a battery of gangliosides and of ganglioside derivatives on (a) CD4 masking; (b) cholera toxin binding (as a well known ganglioside‐protein interaction) and (c) inhibition of lymphocyte mitogenic proliferation (as a second ganglioside interaction with a lymphocyte surface target). Our results indicate that the three interactions are distinctly different, since ganglioside chemical groups which are essential for one of the interactions are irrelevant for the others, and lead to the conclusion that gangliosides can interact with lymphocyte surface targets in a number of ways, causing a number of independent biological effects.
Interleukin 4 activates human B lymphocytes via transient inositol lipid hydrolysis and delayed cyclic adenosine monophosphate generation
Authors: Finney Michael , Guy Graeme R. , Michell Robert H. , Gordon John , Dugas Bernard , Rigley Kevin P. , Callard Robin E. 
Published: March 2007

AbstractWe report from three independent centers that, in human tonsillar B lymphocytes, human IL4 switches on a series of second messenger changes, the precise sequence of which constitutes a novel signal transduction cascade. It involves an immediate and transient elevation of inositol 1,4,5‐trisphosphate and Ca2+ levels. This is followed several minutes later by a sustained rise in cellular cyclic adenosine monophosphate concentration, the triggering of which involves both the Ca2+ rise and an additional, as yet unidentified, IL4‐generated signal. Both the products of the initial inositol lipid hydrolysis and the delayed cyclic adenosine monophosphate accumulation are essential for the later induction of CD23 expression, a major phenotypic change promoted in these cells by IL4. The striking contrast between these findings and those that have been observed for the IL4 triggering of murine B cells is discussed.
Immunodeficient mice recover from infection with vaccinia virus expressing interferon‐γ
Authors: Kohonen‐Corish Maija R. J. , King Nicholas J. C. , Woodhams Cathy E. , Ramshaw Ian A. 
Published: March 2007

AbstractRecombinant vaccinia viruses (VV)‐encoding murine interferon‐γ (IFN‐γ) were constructed and the effect of virus‐encoded IFN‐γ on the immune response towards VV in vivo investigated. In athymic nude mice and sublethally irradiated euthymic mice, IFN‐γ expression by VV enabled the mice to recover from the infection, whereas mice infected with the control virus died. In normal CBA/H mice also, the growth of VV was greatly reduced and it was cleared faster from mouse organs than the control virus. Natural killer (NK) cell responses in these mice were not enhanced suggesting that this recovery is not NK cell mediated. Other possible mechanisms and implications of this observation are discussed.
In vivo cytokine gene expression in T cell subsets of the autoimmune MRL/Mp‐lpr/lpr mouse
Authors: Murray Lesley J. , Lee Rozanne , Martens Christine 
Published: March 2007

AbstractExpression of cytokine genes in freshly isolated T cell subsets in the autoimmune lpr mouse has been studied to determine what factors may be produced by these cells in vivo. RNA prepared from T cell subsets from diseased lpr mice and from the normal congenic strain, MRL/n, was tested for the presence of cytokine‐specific message using the polymerase chain reaction. Cells of the expanded abnormal T cell subset were shown to express genes encoding interferon (IFN)‐γ, tumor necrosis factor (TNF)‐β,TNF‐α and interleukin (IL) 6, cytokines which are associated with inflammatory immune responses. These cells may thus play an important role in exacerbation of the pathological symptoms of the systemic autoimmune disease. These cells expressed no detectable IL 1, IL 2, IL 3, IL 4 or IL 5. Phenotypically normal CD4+ and CD8+T cells from both lpr and MRL/n also contained transcripts for IFN‐γ, TNF‐α, TNF‐β and IL 6. IL 2 mRNA was found almost exclusively in the CD4+ subset, indicating that the CD8+ T cells in the lpr mouse are not highly activated through their class I major histocompatibility complex molecules to produce IL 2, as could occur if a virus infection was inducing autoimmunity in these mice. Similar levels of IL 2 mRNA were present in the CD4+ T cells of lpr and MRL/n mice, demonstrating that these cells are not defective in IL 2 production in vivo.
Metabolic inhibitors distinguish cytolytic activity of CD4 and CD8 clones
Authors: Strack Peggy , Martin Carla , Saito Saburu , Dekruyff Rosemarie H. , Ju Shyr‐Te 
Published: March 2007

AbstractThe effect of various metabolic inhibitors on the expression of cytolytic activity of CD4 (TH1) and CD8 (CTL) clones was studied. The cytolytic activity of CD4 clones, but not CD8 clones, was sensitive to the RNA synthesis inhibitor actinomycin D and the protein synthesis inhibitor cycloheximide. Conversely, cholera toxin (CT) inhibited cytolytic activity of CD8, but not CD4 clones. Both mitomycin C, a DNA synthesis inhibitor, and cyclosporin A (CsA) failed to inhibit the cytolytic activity of either CD4 or CD8 clones.Although pretreatment with CsA or CT did not inhibit the cytolytic activity of CD4 clones, lymphokine (interleukin 2, IL 2, interferon‐γ, IFN‐γ, and tumor necrosis factor, TNF) production was strongly inhibited. Similarly, pretreatment of a CD8 clone with actinomycin D or CsA inhibited lymphokine production without affecting cytolytic activity. The production of mRNA for TNF and IFN‐γ by concanavalin A‐activated CD4 clones was also inhibited by CsA and CT. Moreover, perforin‐specific mRNA was not detected in activated CD4 clones. Collectively, these observations demonstrated that de novo synthesis of RNA and protein is required for expression of cytolytic activity of CD4 clones, yet production of TNF, INF‐γ, IL 2 and perforin is not involved. In contrast, the cytolytic machinery of CD8 clones is present prior to activation and is quickly expressed following activation even when de novo synthesis of RNA, protein and lymphokines is blocked.
Monoclonal antibodies reacting with the interleukin 1 receptor define a multi‐molecular complex
Authors: Lewis Cynthia , Mazzei Gonzalo , Shaw Alan 
Published: March 2007

AbstractBy sequential immunization with a variety of different interleukin (IL) 1 receptor (IL 1R)‐bearing cells and by generating a large number of clones from a single fusion experiment, we have managed to produce two monoclonal antibodies which react with the lymphocyte IL 1R. The antibodies also react with the mouse fibroblast line, 3T3, but we have not yet defined their reactivity with cells carrying low‐affinity receptors. Immunoprecipitation allows the IL 1R to be isolated from EL4 6.1 cell membrane preparations and shows that the IL 1R exists as a complex. The antibodies clearly interfere with IL 1 responses both in vitro and in vivo. These are the first anti‐mouse IL 1R antibodies to be described which clearly and profoundly affect the immune response.
Detection of primary cytotoxic T lymphocytes specific for the envelope glycoprotein of HIV‐1 by deletion of the env amino‐terminal signal sequence
Authors: McChesney Michael , Tanneau Françoise , Regnault Armelle , Sansonetti Philippe , Montagnier Luc , Kieny Marie Paule , Rivière Yves 
Published: March 2007

AbstractA heterogenous population of envelope glycoprotein‐specific cytotoxic effector cells are found in the peripheral blood of individuals infected with HIV‐1, and in many cases env‐specific lysis is not restricted by MHC molecules and is not blocked by antibody to CD3 (Rivière, Y. et al., J. Virol. 1989. 63: 2270). In order to detect env‐specific cytotoxic T lymphocytes (CTL) in fresh peripheral blood mononuclear cells of HIV‐1‐infected donors, a mutant env gene with deletion of the amino‐terminal signal sequence was inserted into vaccinia virus. This deletion of the amino‐terminal signal sequence was inserted into vaccinia virus. This deletion results in synthesis of an envelope protein that is not glycosylated and not expressed at the surface of infected cells. Target cells infected with this recombinant vaccinia virus are not lysed by antibody‐mediated cellular cytotoxicity, but they are recognized by secondary CTL. Comparing lysis of target cells expressing gp160 of HIV‐1 and the signal peptide deletion mutant, primary env‐specific CTL were detected in some individuals infected with HIV‐1.
Inhibition of antibody formation by receptor cross‐linking: the molecular characteristics of inhibitory haptenated polymers
Authors: Dintzis Renée Z. , Okajima Masako , Middleton Marjorie H. , Dintzis Howard M. 
Published: March 2007

AbstractPrevious studies from this laboratory have reported on the characteristics of a molecule which make it inhibitory. These findings were based on studies using the T cell‐independent haptenated polymer, 2,4‐dinitrophenyl‐polyacrylamide (DNP‐PA). The present study was undertaken to determine whether the same molecular properties which defined the inhibitory potentials of DNP‐PA were characteristic of other haptenated polymers as well. The molecules studied here consisted of a series of five diverse fluoresceinated polymers with varying molecular mass and hapten valence. In agreement with the previous findings on DNP‐PA, definable molecular forms of fluoresceinated dextrans, Ficolls, polyacrylamides, carboxymethyl celluloses and polyvinyl alcohols were each found to be capable of inhibiting the anti‐fluorescein response to immunogenic forms of haptenated polymers of either the same or different carrier chemistry. This inhibitory ability was relatively independent of the chemical composition and conformation of the carrier polymer. These studies allow some logical generalizations to be made as to which quantitative molecular properties of haptenated type 2 T cell‐independent antigens determine whether they will be stimulatory or inhibitory of an anti‐hapten immune response.
Interleukin 6 production in the central nervous system during experimental autoimmune encephalomyelitis
Authors: Gijbels Koen , van Damme Jo , Proost Paul , Put Willy , Carton Herwig , Billiau Alfons 
Published: March 2007

AbstractInterleukin 6 (IL6) is one of the major inflammation‐associated cytokines. Elevated serum or tissue levels of IL 6 have been reported to occur in several human diseases, including infections of the central nervous system (CNS), but not in non‐infectious CNS inflammation, e.g. multiple sclerosis. While studying experimental autoimmune encephalomyelitis (EAE) as an animal model for autoimmune inflammation of the CNS, we found increased IL 6 levels in the CNS of mice suffering from a lethal form of the disease. IL 6 levels in the spleens and sera were not significantly increased. These findings are indicative of local production of IL6 in the CNS during EAE, and represent the first demonstration of IL6 production in non‐infectious CNS inflammatory disease.
Recombinant C5a enhances interleukin 1 and tumor necrosis factor release by lipopolysaccharide‐stimulated monocytes and macrophages
Authors: Cavaillon Jean‐Marc , Fitting Catherine , Haeffner‐Cavaillon Nicole 
Published: March 2007

AbstractLipopolysaccharide (LPS) is a potent inducer of interleukin 1 (IL 1) synthesis and release, and of tumor necrosis factor (TNF) secretion. Many signals can enhance the LPS‐induced production of these cytokines. We have previously observed that addition of low amounts of normal human serum to the culture medium enhances IL 1 production. Among serum factors, anaphylatoxins C3a and C5a and/or their desArg derivatives have been shown to enhance LPS‐induced IL 1 and TNF production. However, the capacity of natural anaphylatoxins to induce by themselves the production of cytokines remains a controversal issue. We have investigated the capacity of human recombinant C5a (hrC5a) to induce IL 1 and TNF production. Despite its lack of direct triggering, hrC5a was able to act synergistically with LPS, leading to higher IL 1 and TNF release by human monocytes and mouse peritoneal macrophages. As assessed by the comitogenic assay, hrC5a increased IL 1 release, whereas cell‐associated IL 1 activity was not significantly modified. Measurement by enzyme‐linked immunosorbent assay of human IL 1β led to similar conclusions, whereas measurement of IL 1α by radioimmunoassay indicated, in addition, an increase in intracellular IL 1α.
Difference in the clustering of complement receptor type 1 (CR1) on polymorphonuclear leukocytes and erythrocytes: Effect on immune adherence
Authors: Paccaud Jean‐Pierre , Carpentier Jean‐Louis , Schifferli Jürg Alfred 
Published: March 2007

AbstractComplement receptor type 1 (CR1) mediates the adherence of complement‐reacted immune complexes (IC) to various blood cells. On the erythrocyte, CR1 are clustered, a distribution which favors efficient multivalent binding of C3b‐coated IC. IC can also bind to CR1 expressed on polymorphonuclear (PMN) leukocytes. To evaluate the respective importance of these two cell types in immune adherence reactions, functional analysis of IC binding, as well as morphological studies of CR1 distribution at their surface were undertaken. At equal cell concentrations, resting PMN leukocytes bound the same percentage of IC as erythrocytes, despite expressing four times more CR1 at their surface. At equal CR1 concentrations, IC binding to resting or formyl‐methionyl‐leucyl‐phenylalanine (fMLP)‐stimulated PMN leukocytes was always lower than to erythrocytes. The morphological counterpart of these differences was studied by label‐fracture immunoelectron microscopy. On erythrocytes, almost 50% of the CR1 were distributed in clusters of ⩾ 3 units, while < 15% were grouped in such clusters on the surface of PMN leukocytes. Activation of PMN leukocytes by fMLP increased the surface density of CR1, but the proportion of clustered CR1 remained unchanged.These observations suggest that the low responsiveness of PMN leukocytes towards C3b‐coated IC may be due to the unaggregated state of CR1. In the circulation, erythrocytes might function as a “buffer” for PMN leukocytes, which would otherwise engage too swiftly in reactions with IC.
Activated but not resting T cells or thymocytes express colony‐stimulating factor 1 mRNA without co‐expressing c‐fms mRNA
Authors: Cerdan Chantal , Courcoul Marianne , Razanajaona Diane , Pierrès Anne , Maroc Nicolas , Lopez Marc , Mannoni Patrice , Mawas Claude , Olive Daniel , Birg Françoise 
Published: March 2007

AbstractFollowing the observation that, besides acute myeloid leukemia cells, acute lymphoid leukemia cells of either B or T phenotype could express the transcript for the colony‐stimulating factor 1 (CSF‐1), a growth factor known to be restricted to the monocytic‐macrophage lineage, various sources of resting and/or activated T cells and thymocytes were screened for expression of this hemopoietic growth factor. We report here that the CSF‐1 transcript was rapidly (7 h) induced in T cells by a variety of stimuli, but was not detectable in either resting T cells or thymocytes. In addition, secretion of CSF‐1 was detectable in the supernatants of activated T cells by 72 h, with a peak around 92‐120 h. In contrast to activated monocytes, the transcript of the c‐fms proto‐oncogene, the product of which is the receptor for CSF‐1, was not detectable in either resting or activated T cells. This observation could be relevant to the intimate relationships between T cells and antigen‐presenting cells during immune responses.