bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo interleukin 6 gene expression in the tumoral environment in multiple myeloma
Authors: Portier Marielle , Rajzbaum Gérald , Zhang Xue Guang , Attal Michel , Rusalen Christiane , Wijdenes John , Mannoni Patrice , Maraninchi Dominique , Piechaczyk Marc , Bataille Régis , Klein Bernard 
Published: March 2007

AbstractWhether interleukin 6 (IL6) is an autocrine or paracrine myeloma cell growth factor in vivo remains unresolved. To identify which cells are producing IL 6 in vivo, we have studied the IL 6 gene expression in bone marrow mononuclear cells (BMMC) of 19 patients with multiple myeloma (MM) and in peripheral blood mononuclear cells (PBMC) of 9 patients with plasma cell leukemia (PCL). We found that the IL 6 gene was transcribed by BMMC of most patients with MM (79%). Further, IL 6 mRNA was not produced by purified myeloma cells from patients with either MM (5 patients) or PCL, but by the bone marrow environment, mainly by monocytes and myeloid cells (CD13+CD15+ cells). For 2 patients with PCL, for whom PBMC and BMMC samples were available, IL 6 mRNA could be detected in BMMC but not in PBMC. Finally, no IL 6 mRNA was detected in five freshly established IL 6‐dependent myeloma cell lines. The present data give a clear‐cut demonstration of the paracrine origin of IL 6 in vivo in human MM.
Obtention of a human primary humoral response against schistosome protective antigens in severe combined immunodeficiency mice after the transfer of human peripheral blood mononuclear cells
Authors: Mazingue Christine , Cottrez Françoise , Auriault Claude , Cesbron Jean‐Yves , Capron André 
Published: March 2007

AbstractPeripheral blood mononuclear cells (PBMC) from healthy donors were injected into C.B.‐17 severe combined immunodeficiency (scid) mice which were subsequently immunized with crude Schistosoma mansoni adult worm antigenic preparation (SWAP) or with recombinant S. mansoni 28‐kDa glutathione transferase (r‐Sm‐28‐GST) antigen. PBMC from a S. mansoni‐infected patient were also transfered. The specific human anti‐SWAP and anti‐Sm‐28‐GST antibody responses were monitored. The presence in both cases of human specific antibodies in scid mouse sera was determined by enzyme‐linked immunosorbent assay and Western blotting techniques using anti‐human immunoglobulin reagents. No antibodies were detected in these sera using anti‐mouse immunoglobulin antisera. These antibodies were functional since a cytotoxic activity against schistosomula was observed when monocytes were incubated with scid mouse sera positive for anti‐Sm‐28‐GST antibodies.
Differential regulation of antigen presentation in high‐ and low‐IgE responder mice
Authors: Rizzo Luiz V. , Umetsu Dale T. , Dekruyff Rosemarie H. 
Published: March 2007

AbstractStrains of mice differ greatly in their capacity to produce interleukin (IL) 4 and high levels of serum IgE. The contribution of macrophages (Mϕ) in enhancing the production of IL 4 by T cells in high‐IgE responder mice was studied. Mϕ from BALB/c mice (high‐IgE responder strain) developed an augmented capacity to present antigen to IL 4‐producing T helper type 2 (Th2) clones, when the Mϕ were pretreated by exposure to the lymphokines IL 4 and IL 5. In contrast, identical treatment of Mϕ from H‐2‐identical DBA/2 mice (low‐IgE responder strain) resulted in inhibition of the capacity to stimulate Th2 clones. The impairment of antigen presentation by DBA/2 Mϕ was closely paralleled by a decrease of cell surface class II major histocompatibility complex (MHC) expression and an abrogation of IL 1 production by these cells, while identical treatment of BALB/c Mϕ enhanced class II MHC expression and did not inhibit secretion of IL 1. Our studies demonstrate that IL 4 and IL 5 can exert different effects on Mϕ from high‐ and low‐IgE responder strains of mice, resulting in down‐regulation of the expansion of IL 4‐producing cells in low‐ but not high‐IgE responder mice.
T cell receptor/CD3 and CD28 use distinct intracellular signaling pathways
Authors: Van Lier René A. W. , Brouwer Miranda , De Groot Els , Kramer Ijsbrand , Aarden Lucien A. , Verhoeven Arthur J. 
Published: March 2007

AbstractLigation of the T cell membrane antigen CD28 strongly enhances cytokine secretion in human T lymphocytes that are activated via T cell receptor (TcR)/CD3 or CD2 molecules. This study was undertaken to investigate whether, as has been indicated for activation via TcR/CD3, stimulation via CD28 is dependent on the activation of protein kinase C (PKC). Two inhibitors of PKC, 1‐alkyl 2‐methyl‐glycerol and staurosporine, caused a dose‐dependent inhibition of T cell proliferation induced by anti‐CD3 monoclonal antibodies (mAb). The induction of interleukin (IL)2 secretion was found to be more sensitive to the effects of the PKC inhibitors than the up‐regulation of IL2 receptor expression. In marked contrast, the anti‐CD28 mAb‐mediated enhancement of T cell proliferation and IL 2 secretion were insensitive to the action of either compound. We conclude that two independent signaling pathways may be operational in human T cells. The first used by TcR/CD3 depends on the activation of PKC, whereas the second is employed by CD28 and functions independently of PKC.
Expression of different CD8 isoforms on distinct human lymphocyte subpopulations
Authors: Moebius Ulrich , Kober Gabriela , Griscelli Anne Lise , Hercend Thierry , Meuer Stefan C. 
Published: March 2007

AbstractHuman CD8+ lymphocyte subpopulations were analyzed for their expression of CD8 α and CD8 β subunits. Investigations with uncloned peripheral blood lymphocytes as well as cloned human natural killer and T cell subpopulations demonstrate that CD3− natural killer cells, T cell receptor γ/δ, and CD4+CD8+ T cell clones express exclusively CD8 α gene products. Structural analysis of CD8 molecules demonstrates that CD8 α+/β− T lymphocytes surface express 75‐kDa CD8 α/α homodimers whereas CD8 α/β lymphocytes express concomittantly two CD8 isoforms of different molecular masses (67 kDa and 75 kDa, respectively). Peptide mapping of these latter two isoforms suggests that CD8 is expressed as α/α homodimers and α/β heterodimers on CD8 α/β+ cells. Importantly, we found that the two CD8 isoforms behave functionally different. Thus, in contrast to CD8 α/β+/CD8 α/α+ T lymphocytes, cytolytic activity of CD8α/β−/CD8 α/α+ T cell clones was not inhibited by anti‐CD8 monoclonal antibodies and the latter were not induced to proliferate following CD3/CD8 cross‐linking.
A monoclonal antibody blocking the Schistosoma mansoni 28‐kDa glutathione S‐transferase activity reduces female worm fecundity and egg viability
Authors: Xu Chuan‐Bo , Verwaerde Claudie , Grzych Jean‐Marie , Fontaine Josette , Capron André 
Published: March 2007

AbstractThe protective effects of two different monoclonal antibodies (mAb) raised against the Schistosoma mansoni 28‐kDa glutathione S‐transferase (Sm 28 GST) were investigated. Two mAb of the same isotype (IgM) have been selected according to the blocking effect on Sm 28 GSTenzymatic activity (S13) or the lack of blockade (H12). When passively transfered into Fischer rats, both S13 and H12 significantly reduced the worm burden. In BALB/c mice clear effects on female worm fecundity and egg viability were observed when the S13 mAb was transfered; these effects included significantly reduced loads of intestinal eggs, reduced egg hatching rates and an increased proportion of non‐living eggs. No effect on egg production and egg hatching was observed in H12‐treated mice. In addition, worm pairs recovered from S13‐but not H12‐treated mice laid significantly fewer eggs in vitro, and normal worm pairs incubated in vitro with the S13 mAb produced significantly fewer eggs than those incubated with H12 mAb. The impairment of egg hatching ability was also reproduced in vitro by the S13 mAb. These data suggest the existence of two different effector mechanisms induced by immunization with Sm 28 GST. The effect on the schistosome worm burden appears to be independent of GST activity whereas the effect on S. mansoni female fecundity and egg viability seems to be significantly linked to the inactivation of the enzymatic site.
Preferential development of pre‐B lymphomas with drastically down‐regulated N‐myc in the Eμ‐ret transgenic mice
Authors: Iwamoto Takashi , Pu Meiyi , Ito Masafumi , Takahashi Masahide , Isobe Ken‐Ichi , Nagase Fumihiko , Kawashima Kohei , Ichihara Masatoshi , Nakashima Izumi 
Published: March 2007

AbstractWe established one transgenic mouse line which developed pre‐B leukemic lymphomas by introducing ret cDNA driven by the SV40 promoter and the mouse immunoglobulin (Ig) enhancer. Lymphomas developed not only in the lymph nodes and the spleen but also in the thymus between the ages of 7 and 21 weeks. Analyses of cell surface phenotypes and Ig gene rearrangement revealed that these tumors were surface IgM−B220+ pre‐B lymphomas. The rearrangement pattern of the Ig heavy chain locus indicated that the tumor cells were mono‐ or oligoclonal. Northern blot analysis showed that the ret transgene was expressed at a high level not only in the tumors but also in the prelymphomatous lymphoid tissues. We found that the expression of N‐myc was dramatically down‐regulated in the tumor cells, while the expression of c‐myc was rather stable. Further experiments demonstrated that ret gene product did not directly down‐regulate the expression of N‐myc in transformed pre‐B cell lines by in vitro transfection assay. From these results, we conclude that under the control of Ig enhancer, the ret transgene affected B lymphocytes at the early maturation stage as a prerequisite for transformation, preferentially generating a unique maturation stage of pre‐B lymphomas whose N‐myc expression was developmentally down‐regulated.
The human immunoglobulin x locus. Characterization of the duplicated O regions
Authors: Pargent Walter , Meindl Alfons , Thiebe Rainer , Mitzel Sabine , Zachau Hans G. 
Published: March 2007

AbstractTwo large regions of the human immunoglobulin x locus, the so‐called O regions, have been characterized on cosmid and phage λ clones. The two regions are very similar but not identical duplicates belonging to the Cx proximal (p) and the distal (d) copies of the x locus. The Op and Od regions comprise contigs of 90 and 120 kb, respectively, and contain 20 Vx genes and pseudogenes which have been sequenced. Three pairs of Vx genes were found to be practically identical in the duplicates while allotypic differences, at least for two of the genes, are considerable. The similarities between the duplicate genes may be related to the fact that the two copies of the x locus are arranged in a palindrome‐like fashion with the 5′ sides of the O regions pointing towards each other (CxJx B Lp Ap Op‐Od Ad Ld). This may have contributed to equalizing the sequences. Beyond Op and Od no further Vx genes were found within about 80 kb. Instead, repetitive DNA sequences have been localized there, the structures of which suggest that they may have been involved in the evolution of the Vx gene‐containing regions. The Vx pseudogene containing W regions, that had been transposed in evolution from the short to the long arm of chromosome 2 by a pericentric inversion, may have been derived from the O regions according to structural homologies between defined sections of the O and W regions.
Comparative studies of decay‐accelerating factor and HLA‐DR within the CD8‐brightly positive population
Authors: Tomita Akira , Okada Noriko , Okada Hidechika 
Published: March 2007

AbstractDecay‐accelerating factor (DAF) is a membrane protein that inhibits C3 convertase activity of autologous complement at the cell surface. We found that DAF+ cells and DAF− (DAFlow, if any) cells are clearly separated from each other among CD8‐brightly positive (CD8bright) cells. Using three‐color fluorescence flow cytometry, we found that whereas the CD8brightDAF− population express HLA‐DR (class II major histocompatibility complex antigens, and an activated T cell marker), the CD8brightDAF+ population does not. Therefore, among the CD8bright T cells, DAF and HLA‐DR are mutually exclusive. In addition, the CD8brightDAF+ population proliferates in the presence of recombinant interleu‐kin 2 (rIL2) while the CD8brightDAF− population does not. After a 4‐day cultivation of peripheral blood lymphocytes in the presence of rIL2, expression of HLA‐DR increased in the CD8brightDAF− population and expression of IL 2Rp55 (α chain, the receptor for IL2, and a marker of T cell activation) occurred in the CD8brightDAF+ population. Furthermore, C3 deposition occurred in the CD8brightHLA‐DR+ population which lacks DAF when lymphocytes, that had been cultured for 3 days in the presence of rIL2, were incubated with fresh autologous serum. This result suggests that the absence of DAF on CD8brightHLA‐DR+ T cells might play a role in permitting complement reaction on the cells in vivo and may be related to the regulation of T cell activation.
Isolation and molecular characterization of the B cells producing the paraprotein in a case of benign monoclonal gammapathy in C57BL mice
Authors: Bos Nicolaas A. , Meeuwsen Cornelia G. , De Glopper‐Van der Veer Elisabeth , Van den Akker Theodoor W. , Radl Jiri , Zwaagstra Kornelisje A. , Benner Robbert 
Published: March 2007

AbstractBenign monoclonal gammapathy (BMG) is defined as a benign monoclonal B cell proliferative disorder characterized by the presence of a persisting component of homogenous immunoglobulins (H‐Ig) in the serum. A possible role of antigenic stimulation in the development of BMG has been suggested. From a C57BL mouse, a murine model for BMG, we have Isolated clonally related B cells in order to investigate the occurrence of somatic mutations in the variable heavy chain (VH) region of the genes of H‐Ig‐producing B cell clones. Therefore, B cells were immortalized by hybridoma technology. The hybridomas were screened for resemblance of the serum H‐Ig component by Wieme agar electrophoresis, followed by immunoblotting and isoelectrofocusing. Clonal relationship was investigated by Southern blot analysis using a JH probe. In this way we isolated five hybridomas producing an IgG2a,x that was identical to the original serum H‐Ig component according to testing with anti‐idiotypic antisera. mRNA sequencing of four hybridomas showed only one base pair difference in the VH genes. This particular gene belonged to the J558 VH gene family. When compared to the most closely related known VH sequence, three base pair differences were found. The almost complete absence of base pair differences in the VH genes of the four sequenced hybridomas, compared with an independently derived hybridoma, suggests that the same germ‐line VH gene has been used and that somatic mutations were infrequent in our BMG clone.
Inhibition of interleukin 4‐promoted CD23 production in human B lymphocytes by transforming growth factor‐β, interferons or anti‐CD19 antibody is overriden on engaging CD40
Authors: Gordon John , Katira Anita , Strain Alistair J. , Gillis Steven 
Published: March 2007

AbstractInterleukin 4 (IL4) is an essential component in the sequence of events directing IgE synthesis in uncommitted B lymphocytes. An early consequence of IL4's interaction with the B cell is the induction of CD23, a low‐affinity receptor for IgE (FcϵRII). The present study was designed to explore the detailed regulation of this event. First, we report that transforming growth factor‐β (TGF‐β) is a potent inhibitor of IL4‐promoted CD23 production in human B lymphocytes. The level of inhibition achieved with TGF‐β was greater than that obtained with interferons, or with a monoclonal antibody (mAb) to CD19. Next, we identified three signals, each of which was capable of selectively counteracting the inhibitors of IL 4‐promoted CD23 production: (a) the engagement of surface CD40 antigen with mAb was found to override the influence of all the inhibitors of CD23 expression; (b) mAb to surface IgM overcame the inhibitory actions of TGF‐β and interferons but not that of CD19 ligation; (c) ligation of surface CD72 counteracted the inhibition mediated by TGF‐β but not that generated by interferons or anti‐CD19 antibody. Inhibition of the IL4 signal appeared to be selective for the pathway leading to CD23 induction: none of the inhibitors profoundly altered IL4's ability to enhance surface IgM expression. The study has ramifications for the understanding of events leading to the promotion of IgE synthesis and consolidates the notion of a central role for CD40 in B cell regulation.
Developmental T cell receptor gene rearrangements: Relatedness of the α/β and γ/δ T cell precursor
Authors: Thompson Susan D. , Manzo Andrea R. , Pelkonen Jukka , Larche Mark , Hurwitz Julia L. 
Published: March 2007

AbstractTo examine the relationships between T cell populations at various stages of development, T cell receptor (TcR) gene rearrangements were compared between the four murine populations of (a) early thymocytes, (b) early splenocytes, (c) adult thymocytes and (d) adult splenocytes. TcR α gene rearrangements were shown to progress from 5′ to 3′ regions of the Jα locus and from 3′ to 5′ regions of the Vα locus during the development of T cells in both the thymus and spleen. Thus, the gene rearrangement potentials of proximal genes varied with age, yielding a biased repertoire in the young vs. adult animal. As evidence that γ/δ and α/β gene rearrangements appeared concomitantly in individual precursors, it was found that: (a) multiple adult thymocytes bore α gene rearrangements on one chromosome and δ gene rearrangements on the homologous chromosome, and (b) Vγ3‐Jγ1 rearrangements, prominent joins in the early γ/δ T cell population, were also prominent in the early α/β T cell subset. These data illustrate the non‐random nature of the developmental TcR gene rearrangement and suggest that α/β and γ/δ T cell populations derive from related, if not identical, T cell precursor populations.
Clonal expansion precedes anergy and death of Vβ8+ peripheral T cells responding to staphylococcal enterotoxin B in vivo
Authors: MacDonald H. Robson , Baschieri Selene , Lees Rosemary K. 
Published: March 2007

AbstractStaphylococcal enterotoxin B (SEB) selectively stimulates T cells bearing T cell receptor Vβ8 domains and hence provides a useful model to study immunity and tolerance in vivo. We show here that Vβ8+ T cells in both CD4+ and CD8+ subsets expand dramatically (fivefold) in lymphoid tissues of mice 2–4 days following injection with SEB. This initial clonal expansion, which is accompanied by a transient hyper‐reactivity to SEB, is followed by a rapid decrease in Vβ8+ cells and a concomitant induction of specific non‐responsiveness which persists for at least 30 days. Selective death of Vβ8+ cells occurs during this latter phase. Taken together, our data indicate that clonal expansion, anergy and death can occur as sequential stages of an immune response in vivo.
A Novel surface molecule expressed by long‐term cultured T and natural killer cells is involved in cell activation
Authors: Ferrini Silvano , Cantoni Claudia , Ciccone Ermanno , Biassoni Roberto , Prigione Ignazia , Bottino Cristina , Venzano Paola , Moretta Lorenzo 
Published: March 2007

AbstractTwo monoclonal antibodies (mAb), termed ED6 and LD6, were obtained by immunizing mice with cytotoxic T cell lines expressing the T cell receptor (TcR)γ/δ. These mAb were selected according to their ability to trigger the cytolytic program of the immunizing cell lines in a redirected killing assay. Both mAb recognized molecule(s) expressed on the surface of most long‐term cultured TcR γ/δ+, TcR α/β+ and CD3−CD16+ lymphocytes, while it was absent on resting peripheral blood lymphocytes. In addition both mAb reacted with neoplastic B cell lines, Epstein‐Barr virus‐transformed B cell lines, small cell lung cancer and glioma cell lines, while no surface reactivity was detected on ovarian, breast, colon and non‐small cell lung cancer lines. The functional activity of these mAb was studied by two cytolytic assays. Both mAb were able to trigger the cytolytic program of CD3+TcR γ/δ+ polyclonal cell lines and of a CD3−CD16+ NK cell clone against the murine mastocytoma target cell line P815 (Fc receptor+) in a 4‐h 51Cr‐release assay. In addition, ED6 and LD6 hybridomas were lysed by TcRγ/δ+ effector cells while other hybridomas (obtained from the same fusion) were not lysed. ED6 and LD6 mAb (in the presence of submitogenic doses of the phorbol 12‐myristate 13‐acetate) also induced the secretion of interleukin 2 by ED6/LD6+ T cell clones expressing TcR γ/δ or α/β. mAb‐induced surface antigen modulation experiments showed that the antigenic determinant recognized by ED6 and LD6 co‐modulated, thus indicating that the two mAb probably recognize the same or closely associated molecules. The molecular characteristics of the antigen recognized by the mAb were investigated by Western blot analysis. The LD6 mAb recognized a major band of approximately 65 kDa, both under nonreducing and reducing conditions. These data indicate that ED6 and LD6 mAb recognize a novel non‐lineage‐specific activation antigen which is involved in the induction of the functional program of long‐term cultured T or natural killer cells.
Genetic differences in the T cell receptor alleles of LEW rats and their encephalomyelitis‐resistant derivative, LER, and their impact on the inheritance of EAE resistance
Authors: Blankenhorn Elizebeth P. , Stranford Sharon A. , Smith Paul D. , Hickey William F. 
Published: March 2007

AbstractExperimental allergic encephalomyelitis (EAE) is an animal model for the human disease, multiple sclerosis. The LEW rat strain is very susceptible to induction of EAE, whereas the closely related, major histocompatibility complex (MHC)‐identical, inbred strain LER is resistant. In this report, the two rat strains have been compared for differences at a number of immunologically relevant loci by restriction fragment length analysis and by nucleotide sequencing. A major difference between the two strains was discovered at the T cell receptor β chain locus (TcR β). Both variable (Vβ8) and constant (Cβ1) region elements of TcR β showed allelic variation between LEW and LER.The known genetic influences in rat models of autoimmunity are currently limited to those encoded by the rat MHC, RT‐1. In this study we report our characterization of the allelic differences in TcR β chains between two rats which differ in their susceptiblity to induced EAE, with the goal of understanding the role played by these allelic forms of TcR in the pathogenesis of EAE. The importance of the TcR β allelic difference in resistance or susceptibility to EAE was assessed in a study of backcross rats scored for both EAE and for the novel LER TcR β allele. We found that the TcR β allele from the susceptible strain was present in three out of four susceptible rats, suggesting that it is an important, but not the only, genetic factor in EAE. Supporting this conclusion were the observations that 12 of 13 rats with homozygous LER‐derived TCR β alleles were resistant to EAE.