bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of diversity and function of house dust mite‐specific T lymphocyte clones from atopic and non‐atopic donors
Authors: Wierenga Eddy A. , Snoek Mieke , Bos Jan D. , Jansen Henk M. , Kapsenberg Martien L. 
Published: March 2007

AbstractPanels of CD4+CD8− T lymphocyte clones (TLC), specific for house dust mite Dermatophagoides pteronyssinus (Dp) proteins, were generated from the peripheral blood of an atopic Dp‐allergic donor (AD), suffering from severe atopic dermatitis, and a histocompatible non‐atopic donor (NAD). We studied the diversity of TLC within these two panels in search for the possible occurrence of dominant clone types with properties that might be characteristic for the atopic or non‐atopic state. TLC with specificities for at least four different Dp proteins were found within the panel from AD “L” and for at least three different Dp proteins within the panel from NAD “K”. In addition, both panels showed a considerable but comparable restriction diversity within HLA‐DR. Despite the diversity within the panels, all Dp‐specific TLC from AD were found to produce IL 4, after HLA class II‐restricted Dp‐specific stimulation, whereas the TLC from NAD produced no or only minimal amounts of this lymphokine. Only supernatants from stimulated AD TLC could induce IgE secretion by B cells from NAD. Conclusively, these observations do not give evidence for the occurrence of an abnormal Dp‐specific T cell repertoire in AD, but rather suggest aberrant secretion of the IgE‐inducing lymphokine IL 4 by CD4+ Dp‐specific T cells from AD.
Enhanced immunogenicity of recombinant peptide fusions containing multiple copies of a heterologous T helper epitope
Authors: Löwenadler Björn , Svennerholm Ann‐Mari , Gidlund Magnus , Holmgren Erik , Krook Katarina , Svanholm Cecilia , Ulff Suzanne , Josephson Staffan 
Published: March 2007

AbstractWe have examined the immune response against the nonimmunogenic heatstable enterotoxin (STa) of enterotoxigenic Escherichia coli using recombinant fusion proteins containing the STa‐peptide linked to an IgG‐binding analogue of protein A and varying numbers of the T helper epitope 323–339 from ovalbumin (ova). By immunization of inbred strains of mice with a series of STa fusion proteins, containing up to four copies of ova tandemly multiplied, we demonstrated that the anti‐STa antibody response is controlled by ova‐specific T helper cells in a genetically restricted manner. In the responding mouse strains (2 out of 3 tested), the level of antibody production was increased by addition of multiple ova epitopes, the anti‐STa response being considerably higher to fusion proteins containing four than one or two ova epitopes.
IgE‐dependent antigen focusing by human B lymphocytes is mediated by the low‐affinity receptor for IgE
Authors: Pirron Ulrich , Schlunck Tilman , Prinz Jörg C. , Rieber E. Peter 
Published: March 2007

AbstractIn this study we investigated the role of the low‐affinity receptor for IgE (FcϵRII, CD23) on Epstein‐Barr virus (EBV)‐transformed human B cells in the uptake and presentation to T cells of antigen after complexing with IgE. Cloned EBV‐transformed B cells were incubated for 5 h with (4‐hydroxy‐3‐iodo‐5‐nitrophenyl)acetyl (NIP)‐haptenized tetanus toxoid (NIP‐TT) or NIP‐TT complexed with a chimeric human IgE/mouse anti‐NIP monoclonal antibody (IgE × NIP‐TT) and then contacted for 2 min with autologous cloned TT‐specific T cells. Intracellular Ca2+ mobilization in T cells was determined as an early indicator of T cell activation. The antigen‐presenting capacity of B cells was significantly increased by complexing the antigen with IgE. This effect could be selectively reversed in a dose‐dependent manner by blocking the FcϵRII with an anti‐CD23 monoclonal antibody. The IgE‐mediated increased capacity for presenting antigen became particularly evident when B cells were incubated with NIP‐TT or IgE × NIP‐TT for only 1 h at 4 °C, washed and then cultivated for 6 h at 37 °C allowing uptake and processing of the antigen. These results indicate a new role of the FcϵRII/CD23 molecules in the uptake of antigen by APC which might be of importance in the maintenance of an ongoing immune response against allergens.
Alteration of the humoral immune response against muscle acetylcholine receptor by timed administration of α(1 → 3)dextran
Authors: Tong Zhou , Dwyer Donard S. 
Published: March 2007

AbstractPreviously, we discovered a profound idiotypic connectivity among antibodies involved in the immune responses to α(1 → 3)dextran (Dex) and the acetylcholine receptor (AChR). The present studies were undertaken to assess whether these connections represent functional pathways for regulation. It was found that immunization of mice with Dex prior to challenge with AChR reduced the subsequent response to receptor. The timing of the Dex administration was crucial for this effect with a 6‐day delay between Dex and AChR being optimal whereas 0‐or 12‐day delays proved ineffective. The suppressive effect was specific for Dex, as treatment with the closely related, but idiotypically distinct, α(1 → 6)dextran did not diminish the anti‐AChR response. Consistent with functional connections in the AChR‐Dex network, an inverse relationship between anti‐AChR and anti‐Dex antibodies was observed in these studies. Thus, high levels of anti‐AChR antibodies were associated with low levels of anti‐Dex antibodies and vice versa. A similar relationship was observed for serum antibodies from patients with myasthenia gravis. To investigate the mechanism for the antigen‐induced cross‐regulation, hybridomas were constructed from spleen cells of mice treated 6 days earlier with Dex. A variety of idiotypes (Id), anti‐Id and anti‐anti‐Id were obtained from this fusion. In addition, sera from day‐6 mice were examined for the expression of key anti‐Id which might provide regulation in the anti‐AChR response. The main feature of these sera was the presence of EB3‐7‐reactive antibodies which did not bind Dex, and hence were not identical to J558. A monoclonal antibody with similar properties was obtained from the day‐6 fusion (DX6) which had additional binding specificity for anti‐AChR antibodies. Antibodies induced by Dex immunization appear to participate in the crossregulation observed here. Understanding the mechanisms involved in this phenomenon will have important implications for network theory and for prediction of immune responsiveness.
Induction of B cell activities by interleukin 4 is inhibited by a receptor‐specific monoclonal antibody in vitro
Authors: Maliszewski Charles R. , Sato Timothy A. , Bos Tim Vanden , Beckmann M. Patricia , Grabstein Kenneth H. 
Published: March 2007

AbstractThe effects of interleukin (IL) 4 on B cell growth and differentiation are mediated through binding of IL 4 to a specific cell surface receptor. The murine T cell IL 4 receptor (IL 4R) has recently been cloned and monoclonal antibodies (mAb) which bind specifically to the IL 4R have been developed. The ability of two of these anti‐IL 4R mAb (M1 and M2) to inhibit IL 4‐induced B cell functions in vitro was examined. The M1 mAb inhibited the ability of IL 4 to induce B cell proliferation in a dose‐related fashion. The inhibition was specific for proliferation induced by IL 4 in that the antibody did not affect induction of proliferation by IL 1. Similarly, M1 inhibited IL 4‐dependent B cell differentiation as measured by induction of IgG1 and IgE secretion, decreased IgG3 secretion, increased Ia expression, and increased FcϵR (CD23) expression. In contrast, the anti‐IL 4R‐specific mAb M2 had no effect upon any of these activities. The ability of M1 but not M2 to inhibit IL 4‐induced B cell growth and differentiation correlated with the inhibition of binding of radiolabeled IL 4 by M1. These reagents should be valuable tools with which to analyze the involvement of IL 4 in immune responses.
Identification of the intracytoplasmic region essential for signal transduction through a B cell activation molecule, CD40
Authors: Inui Seiji , Kaisho Tsuneyasu , Kikutani Hitoshi , Stamenkovic Ivan , Seed Brian , Clark Edward A. , Kishimoto Tadamitsu 
Published: March 2007

AbstractCD40 is a 45‐kDa glycoprotein expressed on human B lineage cells. Anti‐CD40 induces the proliferation of B cells and the extracellular region of CD40 is related to those of a certain kind of growth factor receptors. Therefore, it has been proposed that CD40 might be a receptor for a molecule involved in the growth regulation of B cells. The cDNA coding for CD40 was transfected into the murine B lymphoma cell line M12 and the murine thymoma cell line EL4. The growth of both M12 and EL4 transfectants expressing human CD40 was inhibited by anti‐CD40. Phorbol 12‐myristate 13‐acetate (PMA) augmented the growth inhibitory effects of anti‐CD40 on transfectants. The CD40 molecule was constitutively phosphorylated not only in human tonsil B cells but also in transfectants expressing CD40. PMA augmented the phosphorylation of CD40 in these cells. These results indicate that in spite of the growth inhibitory effect of anti‐CD40, the augmentative effect of PMA is conserved in CD40+ transfectants and suggest that the transfectant might be useful for the study of signal transduction mechanism through CD40. To investigate which part of the CD40 molecule is important for signal transduction, transfectants expressing mutant CD40 cDNA were established and their growth response to anti‐CD40 was evaluated. The mutant molecule, which had an Ala for Thr substitution at position 234, and the deletion mutants lacking Thr234 were inactive in growth signal transduction, indicating that Thr234 itself or the region around Thr234 is essential for signal transduction through CD40.
Recombinant interleukin 2‐activated natural killer cells regulate IgG2a production
Authors: Amigorena Sebastián , Bonnerot Christian , Fridman Wolf Herman , Teillaud Jean‐Luc 
Published: March 2007

AbstractIn this report we have analyzed the effect of recombinant interleukin 2 (rIL 2) and rIL 2‐activated natural killer (NK) cells on the production of immunoglobulin isotypes by lipopolysaccharide (LPS)‐stimulated spleen cells from nude mice. We found that rIL 2 induced a dose‐dependent increase of IgG2a secretion and a concomitant inhibition of the secretion of other Ig isotypes. The analysis of the phenotype of LPS‐ and LPS+rIL 2‐stimulated nude spleen cells showed the appearance of a Thy‐1+asialo GM‐1+slgM−CD3−CD4−CD8− cell population in the presence of rIL 2. A population with a similar phenotype was generated upon stimulation of spleen cells from nude mice with rIL 2 alone. These cells lysed YAC‐1 cells, did not contain the α or γ transcripts encoding the corresponding T cell receptor chains and are therefore NK cells activated by rIL 2. In co‐culture experiments, these cells selectively increased the secretion of IgG2a by LPS‐stimulated splenocytes from nude mice. The IgG2a induction triggered by rIL 2‐activated NK cells, as well as that triggered by rIL 2, were blocked by an anti‐interferon γ monoclonal antibody. Thus, rIL 2 activated‐NK cells enhance the production of IgG2a by secreting interferon‐γ.
Resistance to lymphoid engraftment in lpr recipients of normal bone marrow: characterization of chimeric stem cell, monocyte and peripheral lymphoid lineages
Authors: Glaser Roseann M. , Marshak‐Rothstein Ann 
Published: March 2007

AbstractLethally irradiated MRL/lpr mice reconstituted with T cell‐depleted bone marrow stem cells from the non‐autoimmune strain A. Thy had been shown to develop a state of long‐term split chimerism; erythrocytes were derived from the A. Thy donor, while peripheral lymphocytes were derived from the lpr recipient. In contrast, recipients of the non‐lpr‐congenic strain, MRL/+, were fully repopulated in both lineages by donor‐derived hematopoietic cells. In order to more fully understand the mechanisms responsible for this type of split chimerism, we have investigated additional genetic and developmental parameters. We found that histocompatible normal B cell precursors engrafted C3H/HeJ and C57BL/6/+ mice much better than they engrafted the corresponding lpr congenic strains, indicating that resistance to lymphoid engraftment was not unique to the MRL background. Bone marrow cells and peritoneal macrophages were found to express the donor H‐2 phenotype in both non‐lpr and lpr recipients, limiting resistance to the lymphoid lineage. Moreover, we showed that normal bone marrow stem cells passaged in an lpr host environment were subsequently able to repopulate the B cell lineage of non‐lpr secondary recipients, proving that prelymphoid stem cells were intact. Although lymph node cells from A. Thy → MRL/lpr chimeras were lpr‐derived, they did not show the abnormal surface marker expression associated with the lpr phenotype, nor did they develop lymphoid hyperplasia or elevated autoantibody levels. However, A. Thy → MRL/lpr chimeras differed from normal mice in that their spleens were markedly deficient in IgM+ B cells.
Interleukin 6 is a differentiation factor for human megakaryocytes in vitro
Authors: Kimura Hideo , Ishibashi Toshiyuki , Uchida Tatsumi , Maruyama Yukio , Friese Paul , Burstein Samuel A. 
Published: March 2007

AbstractThe response of cells of the megakaryocytic lineage to interleukin 6 (IL 6), a cytokine with multiple biological activities, was studied by adding the factor to human bone marrow (BM) cultures. IL 6 alone had no effect on megakaryocytic colony formation in methylcellulose; however, in the presence of maximally stimulating concentrations of IL 3, almost a twofold increment in colony formation was observed. Tritiated thymidine suicide studies of BM incubated for 2 h with growth factors showed that almost one‐half of megakaryocytic progenitors (CFU‐Mk) preincubated with IL3 or IL3 plus IL6 were in S phase, whereas BM incubated with IL 6 alone was similar to control (∽ 24% of CFU‐Mk in S phase). When ≧ 1 ng/ml of IL6 was added to liquid suspension cultures of BM, the size of individual megakaryocytes was significantly augmented compared with that seen in control cultures. Moreover, the DNA content of megakaryocytes grown in the presence of IL6 was increased (modal ploidy 16N) compared with cultures grown with IL3 (modal ploidy 8N). To determine if the effect of IL6 could be direct rather than mediated via accessory BM cells, the factor was added to cultures of isolated single megakaryocytes. Seventy‐one percent of cells increased in diameter in the presence of IL6, while only 27% increased in size in the absence of the factor. The data show that IL6 is a direct maturation factor for human megakaryocytes, promoting increments in size and ploidy of these cells.
The human intracellular Mx‐homologous protein is specifically induced by type I interferons
Authors: Von Wussow Peter , Jakschies Detlef , Hochkeppel Heinz‐Kurt , Fibich Christian , Penner Lothar , Deicher Helmuth 
Published: March 2007

AbstractThe murine Mx‐1 protein is one of the best biochemically and functionally characterized interferon (IFN)‐induced proteins that is necessary, and sufficient, for providing resistance to murine cells against viral influenza infection. Recently an intracellular human protein homologous to the murine Mx‐1 protein has been identified by means of a specific monoclonal antibody. The restricted induction of this intracellular protein in human mononuclear cells (MNC) by various cytokines was investigated. MNC from 26 of 28 healthy people and 35 of 36 cancer patients before IFN‐α therapy had no detectable Mx‐homologous protein. Incubation of human MNC with IFN‐α and IFN‐β for 24 h at different concentrations led to a dose‐dependent induction of the Mx‐homologous protein. All IFN‐α or IFN‐β preparations tested were equally effective in eliciting this intracellular protein. IFN‐γ induced only 1% of the Mx amount elicited by type‐1 IFN compared on a weight basis. Neither interleukin (IL) 1 nor IL 3, IL 4, IL 5, IL 6, tumor necrosis factor‐α/β, granulocyte colony‐stimulating factor (CSF) or granulocyte macrophage‐CSF at any of the concentrations tested were capable of eliciting any detectable amount of the Mx homolog, while IL 2 was a poor Mx‐homologous protein inducer. In the presence of high‐titered IFN‐α antisera both IL 2 and IFN‐γ were unable to stimulate this protein, proving that IFN‐γ and IL 2 indirectly induce the Mx homolog via IFN‐α. Therefore, the human Mx‐homologous protein is a strictly by type I IFN‐regulated protein in human peripheral blood lymphocytes.
Severe combined immunodeficiency in man with an absence of immunoglobulin gene rearrangements but normal T cell receptor assembly
Authors: Thompson Allan , Hendriks Rudolf W. , Kraakman Margriet E. M. , Koning Frits , Bergh Renée Langlois‐Van Den , Vossen Jaak M. , Weemaes Corry M. R. , Schuurman Ruud K. B. 
Published: March 2007

AbstractAn autosomal recessive type of severe combined immunodeficiency disease (SCID) was characterized by an absence of immunoglobulins (Ig) in the serum and of Ig+ lymphocytes in bone barrow (BM) and peripheral blood. In the BM CD10+/terminal deoxynucleotidyl transferase‐positive lymphocytes were identified. Epstein‐Barr virus‐transformed B lymphoblastoid cell lines (BLCL) obtained from BM and peripheral blood did not synthesize Ig. The Ig heavy and light chain gene complexes in the BLCL had retained the germ‐line configuration. Mature T cells were present but their numbers in peripheral blood were decreased. T lymphoblastoid cells derived from peripheral blood expressed normal T cell receptor (TcR) CD3 complexes and manifested various genomic TcR rearrangements. It was concluded that this type of SCID entailed a complete arrest of B lymphocyte differentiation in an early stage prior to Ig rearrangements and a quantitative defect of T lymphocytes which nevertheless allowed development of mature T cells. Repeated failures of BM transplantation and the striking absence of Ig assembly suggested that this SCID defect resides in the BM microenvironment.
Idiotypic interactions between normal human polyspecific IgG and natural IgM antibodies
Authors: Rossi Françoise , Guilbert Brigitte , Tonnelle Cécile , Ternynck Thérèse , Fumoux François , Avrameas Stratis , Kazatchkine Michael D. 
Published: March 2007

AbstractPooled normal human polyspecific IgG (IVIg) contain anti‐idiotypes against a variety of autoantibodies from patients with autoimmune diseases and IgG autoantibodies present in IVIg. The present study indicates that IVIg may also react through idiotypic/anti‐idiotypic interactions with human natural IgM antibodies. Sixty‐four percent of IgM secreted by B lymphoid cell lines derived from B cells of healthy elderly donors and 18% of IgM secreted by cloned EBV‐transformed cord B cells that were tested, bound through their variable region to F(ab')2 fragments of IVIg. The binding to 2,4,6‐trinitrophenyl (TNP) of a polyreactive IgM with anti‐TNP specificity, was inhibited by F(ab')2 fragments from IVIg, indicating the presence in IVIg of anti‐idiotypes that may interfere with the antibody‐combining site of polyreactive IgM antibodies. The ability of IgM antibodies to interact with idiotypes on IVIg was not related to the degree of polyreactivity of natural antibodies. Our observations further document that IVIg contain antibody specificities against Ig from normal individuals and suggest that IgG originating from the physiologically expressed repertoire may modulate the expression of the potential B cell repertoire. The results may be relevant to the suppressive effect of IVIg in autoimmune diseases.
Structural comparison of α/β and γ/δ T cell receptor‐CD3 complexes reveals identical subunit interactions but distinct cross‐linking patterns of T cell receptor chains
Authors: van Neerven Joost , Coligan John E. , Koning Frits 
Published: March 2007

AbstractHere we compare the subunit interactions within the α/β and γ/δ T cell receptor‐CD3 (TcR‐CD3) complexes. By using different detergent solubilization protocols, subunit interactions can be defined within such cell surface receptor complexes. It was found that in both TcR‐CD3 complexes analogous subunit interactions can be defined: CD3γ and CD3δ each form a stable complex with separate CD3ε chains. Both the TcRγ/δ and TcR α/β form stable receptor complexes with these CD3 γ/ε and CD3 δ/ε subunits. A ζ homodimer is present in these TcR‐CD3 complexes. However, biochemical cross‐linking results in a covalent bond between the CD3γ chain and the TcRβ chain in α/β TcR‐CD3 complexes and between the CD3γ chain and the TcRδ in γ/δ TcR‐CD3 complexes. This latter observation was independent of the type of TcR γ/δ studied (e.g. disulfide or non‐disulfide linked). These cross‐linking results either indicate that the TcR β and δ chains are each others structural homolog or that in TcR‐CD3 complexes both TcR chains (α and β, γ and δ) are spatially closely associated with the CD3γ chain. The identical subunit interactions in the α/β and γ/δ TcR‐CD3 complexes indicate no large structural differences between these receptor complexes but rather suggest a striking conservation of crucial interaction between subunits in the TcR‐CD3 complexes.
In vitro human cytotoxic T cell responses against influenza A virus can be induced and selected by synthetic peptides
Authors: Martinon Frédéric , Gomard Elisabeth , Hannoun Claude , Lévy Jean‐Paul 
Published: March 2007

AbstractStudies on human anti‐influenza cytolytic activities have demonstrated that cytotoxic T lymphocytes (CTL) from HLA‐B37 individuals react preferentially with the peptide corresponding to residues 335–349 of the nucleoprotein, whereas CTL from HLA‐A2 donors recognize peptide 57–68 from the viral matrix as a dominant epitope. We studied the secondary CTL response, obtained from peripheral blood mononuclear cells, of an HLA‐A2+, B37+ individual stimulated either by infectious virus or by synthetic peptides. Only an HLA‐B37‐restricted response was detected after stimulation by the whole virus, showing an immunodominance of this activity over that restricted by HLA‐A2. Moreover, human cytotoxic cell lines were successfully obtained after stimulation of peripheral blood mononuclear cells with synthetic peptides. Under these conditions, it was possible to selectively reveal the existence of an HLA‐A2‐restricted activity directed against the matrix peptide. These results demonstrate that, at least in vitro, it is possible to stimulate a latent repertoire by using synthetic peptides. Nevertheless, we could not induce a response against the matrix or the nucleoprotein peptides in HLA‐A2− or B37− individuals, suggesting that a finer selection of synthetic peptides would be necessary for their possible utilization to induce CTL during vaccination.