bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin‐1‐induced activation of a protein kinase co‐precipitating with the type I interleukin‐1 receptor in T cells
Authors: Martin Michael , Böl Gaby Fleur , Eriksson Anders , Resch Klaus , Brigelius‐Flohé Regina 
Published: March 2007

AbstractWe have investigated the possibility of a protein kinase participating in the signal transduction mechanisms of the interleukin‐1 (IL‐1) type I receptor (IL‐1RI). Our data show that a protein kinase was co‐precipitated with the IL‐1 RI from the two murine T helper cell lines D10N and EL‐4. The kinase activity was detected in an in vitro kinase assay performed with the immuno beads in the presence of exogenous substrates. IL‐1 treatment of the cells resulted in a rapid activation of this protein kinase in a concentration‐dependent manner. Both forms of IL‐1, IL‐1α and IL‐1β, induced this kinase activity, whereas the IL‐1 receptor antagonist (IL‐1ra) was inactive. In excess IL‐1ra competitively antagonized IL‐1 stimulation. In the in vitro kinase assay the exogenous substrates myelin basic protein and histone H1 were phosphorylated, whereas casein or heat‐shock protein HSP27 were not accepted, reflecting a certain selectivity of this protein kinase. The IL‐1RI co‐precipitable protein kinase showed a serine/threonine specificity and was inhibited by staurosporine, but not by inhibitors specific for protein tyrosine kinases or protein kinase C. These results show that a serine/threonine protein kinase directly interacts with the IL‐1RI at the plasma membrane level of T helper cells forming a novel type of IL‐1 inducible signaling complex. This protein kinase may resemble the link coupling the plasma membrane IL‐1 receptor to cytosolic downstream elements in the IL‐1 signaling pathway.
Covalent binding of C3b to monoclonal antibodies selectively up‐regulates heavy chain epitope recognition by T cells
Authors: Santoro Lyse , Drouet Christian , Reboul Angeline , Mach Jean‐Pierre , Colomb Maurice G. 
Published: March 2007

AbstractProtein C3 of the complement system is known for its role in the nonspecific immune response. Covalent binding of C3b to antigen upon complement activation also plays a significant role in specific T cell immune response. C3b‐antigen complexes can bind to complement receptors on the antigenpresenting cell, and the C3b antigen link (most often an ester link) remains fairly stable inside the cells.In this study, IgG1,χ and IgG2a,χ murine monoclonal antibodies (mAb) were used as antigens; covalent complexes between mAb and C3b were produced and puritied in vitro from purified proteins; human B cell lines and T cell clones were raised from tumor patients who received mAb injections for cancer therapy or diagnosis. Recognition of epitopes of these mAb by T cell clones when the mAb were processed alone or bound to C3b was compared.IgG or IgG‐C3b complexes presented by B cell lines were able to stimulate proliferation of χ light chain‐specific T cell clones at similar concentrations. In contrast, IgG‐C3b complex recognition by heavy chain‐specific T cell clones required 100‐fold less IgG‐C3b than uncomplexed IgG. As C3b was shown to be covalently bound only to the IgG heavy chains in the complexes, C3b chaperoning is restricted to only the IgG heavy chain and selectively influences intracellular steps of IgG heavy chain processing. This differential modulation of C3b suggests an early dissociation of IgG heavy and light chains in antigenpresenting cells.
Collagen‐specific cytotoxic T lymphocyte responses in patients with ankylosing spondylitis and reactive arthritis
Authors: Gao Xiao‐Ming , Wordsworth Paul , McMichael Andrew 
Published: March 2007

AbstractBoth ankylosing spondylitis (AS) and reactive arthritis (ReA) are strongly associated with HLA‐B27 although the mechanism for this association is still unknown. Here we examine the hypothesis that B27‐restricted, joint antigen‐specific cytotoxic T lymphocytes (CTL) may be the driving force of AS and ReA. Type II and type XI procollagens (CII and CXI, respectively), expressed almost exclusively in the articular cartilage of the joints, were chosen as the possible targets of autoimmune CTL. Type I procollagen (CI), expressed in many different tissues, was also included as control. Nineteen nonamer peptides bearing appropriate HLA‐B27 binding motifs from human CI, CII and CXI were identified and synthesized. When analyzed for binding affinity to HLA‐B27 in assembly assays, four (two from CII, two from CXI) were found capable of binding to HLA‐B27 with high affinity. These B27‐binding collagen peptides were then used to stimulate peripheral blood lymphocytes from eight B27‐positive AS and three ReA patients for identification of possible B27‐restricted autoimmune CTL. HLA‐B27‐restricted CTL specific for one of the CII peptides, P109 were found in one of the ReA patients, but in none of the others.
Structure of the gene coding for the human early lymphocyte activation antigen CD69: A C‐type lectin receptor evolutionarily related with the gene families of natural killer cell‐specific receptors
Authors: Santis Ana G. , López‐Cabrera Manuel , Hamann Jörg , Strauss Michael , Ánchez‐Madrid Francisco 
Published: March 2007

AbstractCD69 is the earliest inducible cell surface glycoprotein acquired during lymphoid activation. CD69 functions as a signal transmitting receptor involved in cellular activation events including proliferation and the induction of specific genes. This molecule is a member of a supergene family of type‐II integral membrane proteins with C‐type lectin domains. We have herein studied the genomic structure of the human gene encoding CD69. The coding sequence is divided into five exons separated by four introns. The first two exons corresponded to separate functional domains of the protein (cytoplasmic tail and the transmembrane region), while the final three exons encoded the carbohydrate‐recognition domain (CRD). The conserved intron position between the exons encoding the CRD indicated that this protein is closely related to other type‐II receptor groups with the C‐type CRD, such as the asialoglycoprotein receptors, the low‐affinity IgE receptor (CD23), and natural killer cell‐specific receptors, NKR‐P1 and Ly49. In contrast to the broad NKR‐P1 and Ly‐49 gene families, CD69 is a single‐copy gene, as demonstrated by Southern blot analyses. The major transcription initiation site has been located, by amplification of cDNA 5′ ends, 30 nucleotides downstream of a consensus TATA box. Comparison of human CD69 and mouse NKR‐P1 gene structures indicates that the first intron maintains a conserved position, suggesting that CD69 and this gene family may diverge from a common ancestor gene. A possible evolutionary pathway of these genes is proposed.
Lymphadenopathy induced by the cooperation between lprcg and gld genes is of lpr but not of gld phenotype
Authors: Matsuzawa Akio , Katagiri Takuya , Ogata Yoshihisa , Kominami Ryo , Kimura Mikio 
Published: March 2007

AbstractMice homozygous for the lpr (lymphoproliferation), lprcg or gld (generalized lymphoproliferative disease) mutation develop strikingly similar lymphadenopathy with expansion of B220+ CD4− CD8− double‐negative (DN) T cells and autoimmunity. To elucidate the roles of bone marrow (BM) and lymph node (LN) in lymphoproliferation, BM and LN were transplanted simultaneously into normal or +/+ mice in various genotype combinations. In lpr/lpr or lprcg/lprcg BM recipients grafted lpr/lpr and lprcg/lprcg LN swelled but +/+ and gld/gld LN atrophied. In gld/gld BM recipients all of LN swelled regardless of genotype. Thus, lpr and lprcg are phenotypically different from gld in the interaction of BM‐derived DN T cells and +/+ LN. Compared with lpr the lprcg gene differs in its ability to complement with gld in induction of lymphadenopathy. To determine whether lymphoproliferation induced by the cooperation between lprcg and gld is of lpr or gld phenotype, LN of various genotypes were implanted into double heterozygous lprcg/+, gld/+ mice. Grafted lpr/lpr and lprcg/lprcg LN swelled but +/+ and gld/gld LN atrophied, indicating that it is of lpr phenotype. Moreover, grafted lprcg/+ LN swelled but lpr/+ LN atrophied, indicating that, in the heterozygous state, lprcg is phenotypically different from lpr as it allows for LN accumulation of DN T cells induced by lprcg‐gld cooperation.
A yeast artificial chromosome contig on mouse chromosome 11 encompassing the nu locus
Authors: Nehls Michael , Lüno Karsten , Schorpp Michael , Krause Sabine , Matysiak‐Scholze Uta , Prokop Christa‐Maria , Hedrich Hans J. , Boehm Thomas 
Published: March 2007

AbstractMutations at the nude locus disrupt the homing process of T cell progenitor cells to the thymic rudiment, a key aspect of T cell differentiation. Here, we map the nude locus to a set of overlapping yeast artificial chromosomes (YAC) clones covering a genetic interval of about 0.5 centi Morgan on mouse chromosome 11. These results provide a suitable starting point to molecularly clone the nude gene.
Interleukins (IL)‐1 and IL‐2 control IL‐2 receptor α and β expression in immature thymocytes
Authors: Wilsonu Anne , Corthésyu Patricia , Reichenbachu Patrick , MacDonaldu H. Robson , Nabholz Markus 
Published: March 2007

AbstractFunctional high‐affinity interleukin‐2 receptors (IL‐2R) contain three transmembrane proteins, IL‐2Rα, β and γ. We have investigated the expression of IL‐2Rα and β genes in immature mouse thymocytes. Previous work has shown that during differentiation these cells transiently express IL‐2Rα on their surface. Stimulation of IL‐2Rα+ and IL‐2Rα− immature thymocytes with phorbol 12‐myristate 13‐acetate and calcium ionophore induces synthesis of IL‐2Rα and IL‐2Rβ mRNA. Most of this response depends on autocrine stimulation by IL‐2. IL‐1 synergizes with IL‐2 to induce a 120‐fold increase in IL‐2Rα mRNA and a 14‐fold increase in IL‐2Rβ mRNA levels. A large proportion of the stimulated cells contains both transcripts. These interleukins do not induce any differentiation to more mature phenotypes. Collectively, these results show that IL‐2 plays a major role in the regulation of IL‐2R expression in normal immature thymocytes. We suggest that this response to interleukins may be part of a homeostatic mechanism to increase the production of immature thymocytes during stress.
New infectious mammary tumor virus superantigen with Vβ‐specificity identical to staphylococcal enterotoxin B (SEB)
Authors: Lutheru Sanjiv , Shakhov Alexander N. , Xenariosu Ioannis , Hagau Satomi , Imaiu Shunsuke , Acha‐Orbea Hans 
Published: March 2007

AbstractOnly few infectious mouse mammary tumor viruses (MMTV) have been characterized which induce a potent superantigen response in vivo. Here we describe the characterization of an MMTV which was isolated from milk of the highly mammary tumor‐prone SHN mouse strain. Exposure of newborn mice to milk‐borne MMTV (SHN) results in a very slow deletion of Vβ7, 8.1, 8.2 and 8.3 expressing peripheral T cells. Subcutaneous injection of adult mice with this virus induces a rapid and strong stimulation of all four affected Vβ‐subsets in vivo. Besides the strong T cell effect we observed an early proliferation and activation of the local B cell pool leading to the initial secretion of IgM followed by preferential secretion of IgG2a, by day 6. Sequence comparison of the polymorphic C terminus with known open reading frames revealed high homology to the endogenous provirus Mtv‐RCS. This is the first report of a virus having a complete overlap in Vβ‐specificity with a bacterial superantigen stimulating as many as 35 % of the whole CD4+ T cell repertoire including Vβ8.2.
Local and systemic consequences of acute, low‐dose ultraviolet B radiation are mediated by different immune regulatory mechanisms
Authors: Shimizuu Tadamichi , Streilein J. Wayne 
Published: March 2007

AbstractAcute, low‐dose ultraviolet B (UVB) radiation alters the local skin site such that epicutaneous application of hapten fails to induce contact hypersensitivity (CH), but induces tolerance in UVB‐susceptible mice. Although the inability of irradiated skin to support CH induction may be a strictly local effect, there may also be systemic immune consequences of UVB radiation delivered in this manner. To examine this matter, abdominal skin of C57BL/6 mice was exposed to acute, low‐dose UVB radiation. Dinitrofluorobenzene was immediately painted directly on the irradiated site, or at a distant (unirradiated) site. In separate experiments, epicutaneous application of the hapten on a distant site was delayed for 1–3 days. The mice were tested for acquisition of CH, and for tolerance, i.e. the capacity to become sensitized when exposed subsequently to hapten via normal body wall skin. It was found that, immediately after completion of the UVB regimen, CH was inducible via unirradiated, but not via irradiated, skin. At 3 days post‐UVB exposure, CH was no longer inducible even through unirradiated skin. Mice that first encountered hapten via UVB‐exposed skin developed tolerance, as did mice that first encountered hapten via unirradiated skin of UVB‐treated mice. Neutralizing anti‐tumor necrosis factor‐α TNF‐α antibodies failed (a) to restore the ability of unirradiated skin to support induction of CH, and (b) to interfere with tolerance induction, whether hapten was first painted on irradiated or unirradiates skin. The data indicate that the acute, low‐dose regimen of UVB radiation produces effects on the immune system that are manifest locally as well as systemically. By demonstrating that the disruption of CH induction following UVB radiation is TNF‐α dependent, whereas locally and systemically induced tolerance is not, our findings encourage further search for other UVB‐related modulators of systemic immunity and tolerance.
Variable region gene usage of human monoclonal rheumatoid factors derived from healthy donors following immunization
Authors: Thompson Keith M. , Randen Ingrid , Børretzen Marie , Førre Øystein , Natvig Jacob B. 
Published: March 2007

AbstractA study was performed to compare the use of immunoglobulin V gene segments by rheumatoid factors (RF) produced in physiological responses following a defined antigenic stimulus, with RF produced in rheumatoid arthritis (RA) and RF produced as monoclonal (M)‐components in certain lympho‐proliferative diseases. A panel of 46 monoclonal RF was produced, using hybridoma techniques, from healthy individuals following immunization with foreign antigens (mis‐matched red blood cells). A panel of previously characterized monoclonal RF from RA synovial tissues was extended to a total of 24 and included in the study. The variable heavy (VH) and variable light (VL) chain gene families used by these RF were determined using idiotypic markers and polymerase chain reaction amplification with VH‐specific primers. The frequencies of expression of the various gene families was compared between the two groups, and compared with the published expression frequencies seen amongst M‐component RF. The majority (87 %) of RF from healthy donors were found with light chains using V gene segments of the Vχ3 family, in conjunction with VH gene segments belonging to the VH1, VH3 and VH4 families. The over‐expression of Vχ3, together with the distribution of VH families, demonstrates close similarities with RF found as M‐components in lympho‐proliferative diseases. In contrast, RF from RA patients showed a predominant use of VH3 gene segments (82 %) and an unbiased expression of Vχ3 segments (29 % of the light chains). These data suggest that RF found as M‐components are representative of RF used in normal physiological responses, but have undergone neoplastic or other transformation. RF found in the synovial tissue of RA patients appear to be driven by different mechanisms than RF seen in physiological responses in healthy individuals.
Protection from experimental autoimmune diabetes in the non‐obese diabetic mouse with soluble interleukin‐1 receptor
Authors: Nicoletti Ferdinando , di Marcou Roberto , Barcelliniu Wilma , Magro Gaetano , Schorlemmeru Hans U. , Kurrleu Roland , Lunettau Michele , Grasso Sebastiano , Zacconeu Paola , Meronif Pierluigi 
Published: March 2007

AbstractWe have evaluated the effects of a treatment with soluble interleukin‐1 receptor (sIL‐1R) in the accelerated model of autoimmune diabetes induced by cyclophosphamide (CY) in the non‐obese diabetic (NOD) mouse. Prior to the CY challenge (350 mg/kg body weight), female euglycemic NOD mice were randomly divided into three groups (A–C). Groups B and C were treated daily from 1 day before to 13 days after the CY challenge with sIL‐1R at doses of 0.2 and 2 mg/kg body weight. Group A was treated with PBS. By 2 weeks after CY administration, an acute form of autoimmune diabetes with glycosuria, hyperglycemia and severe insulitis occurred in the majority (13/20, 65%) of the control mice (group A). In contrast, repeated injections with sIL‐1R protected NOD mice from insulin‐dependent diabetes mellitus (IDDM) development in a dose‐dependent fashion; the incidence of IDDM was 53.3% (8/15) in the mice treated with 0.2 mg/kg and only 6.7% (1/15) in those treated with 2 mg/kg. However, none of the doses of the sIL‐1R reduced the extent of insulitis in NOD mice. Importantly, the anti‐diabetogenic property of sIL‐1R may not involve major T cell function impairment; accordingly, in parallel experiments, splenic lymphoid cells from NOD mice not challenged with CY, but treated with 2 mg/kg sIL‐1R for 5 consecutive days showed a normal distribution of mononuclear cell subsets and maintained their capacity to secrete interferon‐γ and IL‐2 and to proliferate in response to polyclonal mitogenic stimulation with concanavalin A.
Developmental shift in the patterns of interleukin production in early post‐natal life
Authors: Coutinho Graça Cunha , Delassusu Sylvie , Kourilskyu Philippe , Bandeira António , Coutinho António 
Published: March 2007

AbstractIn mice, immunological tolerance to self is established in the perinatal period, when tolerance susceptibility to allogenic tissues is higher than in adults. We have now investigated whether this could result from developmental regulation of effector functions of T cells exposed to specific antigens, by studying the “natural” or T cell receptor‐induced expression of several interleukin genes. We used qualitative and quantitative polymerase chain reaction methods to study interleukin (IL)‐2, IL‐4, IL‐10 and interferon‐γ mRNA expression by splenic cells at different ages. The results show that newborn peripheral cells (up to day 7), in contrast to the T lymphocytes of adult mice, express high levels of IL‐4 and interferon‐γ, and very low levels of IL‐2 messenger spontaneously and upon specific T cell activation. This characteristic phenotype depends on intrinsic T cell properties, as it is not due to the newborn environment.
Presentation of viral antigens restricted by H‐2Kb, Db or Kd in proteasome subunit LMP2‐and LMP7‐deficient cells
Authors: Zhou Xianzheng , Momburgu Frank , Liuu Tianmin , Motalu Ussama M. Abdel , Jondalu Mikael , Hämmerlingu Günter J. , Ljunggren Hans‐Gustaf 
Published: March 2007

AbstractIn the class II region of the major histocompatibility complex (MHC), four genes implicated in MHC class I‐mediated antigen processing have been described. Two genes (TAP 1 and TAP 2) code for multimembrane‐spanning ATP‐binding transporter proteins and two genes (LMP 2 and LMP 7) code for subunits of the proteasome. While TAP 1 and TAP 2 have been shown to transport antigenic peptides from the cytosol into the endoplasmic reticulum, where the peptides associate with MHC class I molecules, the role of LMP 2/7 in antigen presentation is less clear. Using antigen processing mutant T2 cells that lack TAP 1/2 and LMP 2/7 genes, it was recently shown that expression of TAP 1/2 alone was sufficient for processing and presentation of the influenza matrix protein M1 as well as the minor histocompatibility antigen HA‐2 by HLA‐A2. To understand if presentation of a broader range of viral antigens occurs in the absence of LMP 2/7, we transfected T2 cells with TAP 1, TAP 2 and either of the H‐2Kb, Db or Kd genes and tested their ability to present vesicular stomatitis vires and influenza virus antigens to virus‐specific cytotoxic T lymphocytes. We found that T2 cells, expressing TAP 1/2 gene products, presented all tested viral antigens restricted through either the H‐2Kb, Db or Kd class I molecules. We conclude that the proteasome subunits LMP 2/7 as well as other gene products in the MHC class II region, except from TAP 1/2, are not generally necessary for presentation of a broader panel of viral antigens to cytotoxic T cells. However, the present results do not exclude that LMP 2/7 in a more subtle way may, or in rare cases completely, affect processing of antigen for presentation by MHC class I molecules.
Lymphotoxin acts as an autocrine growth factor for Epstein‐Barr virus‐transformed B cells and differentiated Burkitt lymphoma cell lines
Authors: Gibbons Deena L. , Roweu Martin , Cope Andrew P. , Feldmann Marc , Brennan Fionula M. 
Published: March 2007

AbstractA critical event in B cell immortilization by Epstein‐Barr virus (EBV) is the establishment of an autocrine loop where cells produce a growth factor which supports their own proliferation. We investigated the potential of lymphoblastoid cell lines (LCL) and Burkitt lymphoma (BL) cell lines to produce and respond to the cytotoxins, tumor necrosis factor‐α (TNF‐α) and lymphotoxin (LT). Transformation in vitro of peripheral blood B cells by EBV from seven different donors resulted in spontaneous production of both LT (11542 pg/ml ± 7546, mean ± SD) and, to a lesser extent, TNF‐α (197 pg/ml ± 174). Similarly BL cell lines derived from in vivo transformation which developed a ‘LCL‐like’ phenotype in vitro (group III) produced more LT (1990 pg/ml ± 1740) than the ‘group I’ BL cell lines (< 40 pg/ml LT) which had maintained the original BL biopsy cell phenotype in vitro. Transformation of periphreal blood B cells to generate LCL also resulted in an increase in surface p75 (p < 0.02) and to a lesser extent p55 (not significant, ns) TNF receptor (TNF‐R) expression. Similar increases in surface TNF‐R (p75 p < 0.02, p55 ns) were observed on the ‘group III’ BL cell lines compared with the ‘group I’ BL cell lines. Proliferation of an LCL and a ‘group III’ BL cell line in vitro was via an autocrine loop since inhibition of LT reduced proliferation. This proliferation could also be blocked in the presence of the antagonistic anti‐p55 TNF‐R antibody, H398, but not the antagonistic antibody anti‐p75 TNF‐R antibody UTR‐1. Furthermore, proliferation could be induced with the p55 agonistic antibody, HTR‐9. In contrast to these observations with p55 TNF‐R antibodies, two out of six of the ‘group III’ BL lines (Jijoye and Oba) only expressed the p75 TNF‐R and proliferation of these cells could only be blocked by the antagonistic anti‐p75 TNF‐R antibody UTR‐1. These data suggest that LT is an autocrine growth factor for lymphoblastoid cells, and BL cell lines which display an LCL phenotype. Furthermore, although both TNF‐R are increased on the surface of these cells, this autocrine growth signal is mediated principally through binding to the p55 TNF‐R.