bluuebunny/crossref_metadata_2025_split huggingface dataset:
The splenic marginal zone is absent in alymphoplastic aly mutant mice
Authors: Koike Ryuji , Nishimura Toshihide , Yasumizu Ryoji , Tanaka Hisako , Hataba Yoshiaki , Watanabe Toshiki , Miyawaki Shigeki , Miyasaka Masayuki 
Published: March 2007

Abstractaly is a unique spontaneous autosomal recessive mutation in mice that causes a deficiency in the systemic lymph nodes (LN) and Peyer's patches (PP). aly also induces abnormal histological findings in the spleen and a deficiency in humoral and cell‐mediated immune functions, although lymphocytes of the aly/aly mouse show virtually normal immune responses in vitro. We studied the structure of the spleen of aly mice in detail by immunohistochemistry and electron microscopy. We found that the spleen of the aly/aly mouse was deficient in the expression of specific antigens for marginal metallophils (MM), marginal zone macrophages (MZM) and fibroblastic reticular cells (FRC), which are components of the marginal zone (MZ) of the spleen. Morphological analysis indicated that the aly/aly spleen is deficient in the structure of MZ, which may, in part, account for the severe immunodeficiency in the aly/aly mouse. We then performed reciprocal bone marrow transplantation experiments (BMT) between normal and aly mice and found a clear correlation between the formation of LN and the development of the splenic MZ in these mice; i.e. successful development of LN was invariably associated with the appearance of the MZ structure, whereas the failure of LN development was always associated with the absence of the development of MZ. These BMT results suggest that a common factor may regulate the generation of both LN and MZ of the spleen.
Activated B cells express functional Fas ligand
Authors: Hahne Michael , Renno Toufic , Schroeter Michael , Irmler Martin , French Lars , Bornand Thierry , MacDonald H. Robson , Tschopp Jürg 
Published: March 2007

AbstractFas ligand (FasL, Apo‐1L) is a member of the tumor necrosis factor protein family and binding to its receptor (Fas, Apo‐1, CD95) triggers cell death through apoptosis. Ligand expression is restricted to cells with known cytolytic activity and found on hematopoietic cells of the T cell and natural killer lineage. Here we provide evidence that B lymphocytes can express FasL. Flow cytometric analysis revealed that FasL is expressed on the surface of B cells upon stimulation with either lipopolysaccharide or phorbol 12‐myristute 13‐acetate/ionomycin. FasL expression on activated B cells was confirmed by Western blot and reverse transcriptase polymerase chain reaction analysis. FasL on B cells is functional since lipopolysaccharide‐activated B lymphocytes derived from wild type, but not from g/d mutant mice, were able to kill Fas‐sensitive target cells. Our data suggest that the Fas system may contribute to the control of B cell homeostasis.
CD31/PECAM‐1‐driven chemokine‐independent transmigration of human T lymphocytes
Authors: Zocchi Maria Raffaella , Ferrero Elisabetta , Leone Biagio E. , Rovere Patrizia , Bianchi Elisabetta , Toninelli Elisabetta , Pardi Ruggero 
Published: March 2007

AbstractWe assessed the relative contribution of CD31/PECAM‐1 (platelet‐endothelial cell adhesion molecule‐1) to T lymphocyte transmigration by the use of transfected murine fibroblasts stably expressing either the human CD31/PECAM‐1 or the intercellular adhesion molecule‐1 (CD54/ICAM‐1). Unlike CD54/ICAM‐1, CD31/PECAM‐1 supported migration of activated T cells in the absence of chemokines: most of the migrating lymphocytes were CD31+ and displayed a phenotype corresponding to the naive subpopulation (LFA‐1dull and CD45RA+). Migration of activated T lymphocytes through CD54/ICAM‐1+ transfected monolayers could be induced by creating a chemotactic gradient with the chemokine monocyte chemotactic protein‐1, and the migrating cells mainly displayed a memory phenotype (LFA‐1brightCD45RO+) under these conditions. Furthermore, we found that in transfected cells CD54/ICAM‐1 is uniformly distributed along the apical surface of the cells, while CD31/PECAM‐1 is concentrated at the intercellular junctions, suggesting the existence of a haptotactic gradient (i.e. a gradient of substrate‐ or cell‐bound molecules) responsible for T cell migration. This was also confirmed by the finding that monolayers of murine fibroblasts transfected with a CD31/PECAM‐1 mutant lacking the cytoplasmic domain (CD31/PECAM‐1‐Δcyto), which has a reduced tendency to localize at cell‐cell contact areas, supported efficient adhesion but were unable to induce migration of activated T cells unless a chemotactic gradient was created. We propose that in lymphocytes, homophilic CD31/PECAM‐1 adhesion may be primarily involved in transmigration of naive T cells and that its role is complementary to that of CD54/ICAM‐1.
Unique role of thyroxine in T cell recognition of a pathogenic peptide in experimental autoimmune thyroiditis
Authors: Dawe Kim I. , Hutchings Patricia R. , Geysen Mario , Champion Brian R. , Cooke Anne , Roitt Ivan M. 
Published: March 2007

AbstractWe have previously demonstrated the importance of iodination and the requirement of the thyroxine residues in thyroglobulin (Tg) for the stimulation of two clonotypically distinct murine T cell hybridomas reactive against human and mouse Tg. We are now able to show that these T cell hybridomas only recognize an 11‐residue peptide containing a thyroxine structure that has iodine at two positions on each ring. This iodination state is critical for recognition by these hybridomas as a peptide containing de‐iodinated thyroxine is nonstimulatory. Furthermore we have demonstrated that a peptide lacking the thyroxine residue or containing de‐iodinated thyroxine cannot block the recognition of the thyroxine‐containing peptide. We suggest that in our system the thyroxine residue is involved in binding to major histocompatibility complex (MHC) class II molecules. We have also been able to show that the thyroxine residue is available for contact by the T cell receptor (TCR) as recognition of the peptide/H‐2Ak complex is blockable by an antibody directed against thyroxine. Using substituted peptides, we have been able partially to define the residues within the peptide that are critical for recognition of the 11‐residue peptide by our hybridomas. From our data, we suggest that the thyroxine residue may bind the MHC and TCR, while the residues identified in the peptide backbone as important for the stimulation of the hybridomas may bind only the TCR.
Cytotoxic T lymphocytes to Plasmodium falciparum epitopes in an area of intense and perennial transmission in Tanzania
Authors: Lalvani Ajit , Hurt Nicole , Aidoo Michael , Kibatala Patience , Tanner Marcel , Hill Adrian V. S. 
Published: March 2007

AbstractStudies in The Gambia have provided indirect evidence that cytotoxic T lymphocytes (CTL) play a protective role against malaria in humans and recently, using allele‐specific HLA class I peptide motifs, several peptide epitopes for CTL in four pre‐erythrocytic Plasmodium falciparum antigens have been identified in naturally exposed Gambians. However, CTL levels were low, suggesting that boosting these low levels by immunization might provide substantial protection. In the Kilombero valley of Tanzania, malaria transmission is holoendemic and 300 times more intense than in The Gambia. We report here that several of the epitopes identified in The Gambia are also recognized in naturally exposed, partially immune Tanzanian adults and that levels of CTL are similar to or slightly higher than in Gambian subjects, despite the much higher inoculation rate. We report a new HLA‐A2.1‐restricted epitope from the thrombospondin‐related anonymous protein (TRAP) and we demonstrate that peptide epitopes in TRAP are naturally processed for recognition by CTL from naturally exposed humans. The common allele of a variable HLA‐B7‐restricted epitope in the circumsporozoite protein behaved as an altered peptide ligand (APL) with respect to CTL cognate for a rarer allelic variant of this epitope, suggesting that APL antagonism may occur in natural CTL responses to P. falciparum. The moderate levels of CTL observed, even in this area of intense malaria transmission, points to the need to assess candidate vaccines aimed at increasing CTL levels.
CTX, a novel molecule specifically expressed on the surface of cortical thymocytes in Xenopus
Authors: Chrétien Isabelle , Robert Jacques , Marcuz Anne , Garcia‐Sanz Jose A. , Courtet Michèle , Du Pasquier Louis 
Published: March 2007

AbstractCTX, a novel developmentally regulated type‐I transmembrane protein is expressed specifically by a large fraction of cortical thymocytes in the amphibian Xenopus. This apparently monomeric 55‐kDa glycoprotein is composed of two immunoglobulin domains, one variable (V) and one constant (C2 type), followed by a transmembrane and a 64‐amino acid cytoplasmic domain. The first immunoglobulin domain is a V‐J segment that is generated without gene rearrangement. In the genome, the V and C2 domains are both encoded by two half‐domain exons. Two CTX loci are found per haploid genome, and they exhibit sequence differences with a high replacing/silent ratio in the CDR1‐like region of the V domain, suggesting that these differences were selected. The cytoplasmic domain contains a motif that is highly conserved evolutionarily in several types of proteins, including adenylyl cyclases. Based on its unique tissue distribution, the variability of its V region and the motif of its cytoplasmic domain, CTX is a candidate for a new type of specific signaling molecule involved in thymocyte selection.
B cell early response gene expression coupled to B cell receptor, CD40 and interleukin‐4 receptor co‐stimulation: evidence for a role of the egr‐2/krox20 transcription factor in B cell proliferation
Authors: Newton Joshua S. , Li Jin , Ning Zhi‐Qiang , Schoendorf Diana E. , Norton John D. , Murphy John J. 
Published: March 2007

AbstractB lymphocytes are activated following antigen stimulation of the B cell receptor but require co‐stimulation with accessory molecules provided by interleukin (IL)‐4/CD40 ligand for cell cycle progression and proliferation. By analyzing a panel of 11 early response genes induced by cross‐linking of surface immunoglobulin, we show that CD40 signaling alone induces only 2 genes, c‐myc together with an anonymous gene, 3L3, and that these are distinct from the set of genes induced in response to IL‐4. Co‐stimulation with the proliferative combination of anti‐μ, IL‐4 + CD40 signaling led to a fourfold enhancement of egr‐2/krox20 expression over that seen with anti‐μ alone. Egr‐2 expression/activity was selectively inhibited by the immunosuppressive drug cyclosporin A, and antisense oligonucleotide blockade of Egr‐2 activity elicited a dose‐dependent inhibition of B cell proliferation. Taken together, these observations show that the early gene regulatory programs coupled to different surface receptors on B cells are largely distinct from each other, but that certain genes, exemplified by egr‐2, may represent a point of convergence in the integration of different signaling pathways into the B cell proliferative response.
Lymphocyte binding to vascular endothelium in inflamed skin revisited: a central role for vascular adhesion protein‐1 (VAP‐1)
Authors: Arvilommi Anna‐Maija , Salmi Marko , Kalimo Kirsti , Jalkanen Sirpa 
Published: March 2007

AbstractThe binding of leukocytes to vascular endothelium and their migration into tissues is mediated by adhesion molecules on the endothelial cells and leukocytes. Vascular adhesion protein‐1 (VAP‐1) is a 170–180/90‐kDa endothelial molecule expressed most prominently in high endothelial venules in peripheral lymph node (PLN) type lymphatic tissues. VAP‐1 mediates lymphocyte binding to PLN, tonsil and synovium. The expression of VAP‐1 is induced in inflammatory diseases such as arthritis and gut inflammation. We examined the expression, structure and function of VAP‐1 in normal and inflamed skin and compared it to those of other adhesion molecules implicated in skin homing. In psoriasis, lichen ruber planus, pemphigoid and allergic lesions, VAP‐1 was markedly up‐regulated. The expression of VAP‐1 was also increased in biopsies of healthy skin of the patients. The VAP‐1 molecule induced in skin is decorated with abundant sialic acids. VAP‐1 in inflamed skin is functional, since inhibition with anti‐VAP‐1 monoclonal antibodies caused a 60% reduction in lymphocyte adhesion to vascular endothelium. Antibodies against E‐selectin, which has been regarded as the major vascular addressin directing cutaneous lymphocyte traffic, and, surprisingly, against peripheral lymph node addressin (PNAd), caused inhibitions of 30% and 60%, respectively, in the frozen section adhesion assay. These findings suggest important roles also for VAP‐1 and PNAd in lymphocyte homing into inflamed skin.
Proteasome inhibitors block VCAM‐1 and ICAM‐1 gene expression in endothelial cells without affecting nuclear translocation of nuclear factor‐ϰB
Authors: Cobb Ronald R. , Felts Katherine A. , Parry Graham C. N. , Mackman Nigel 
Published: March 2007

AbstractEndothelial cells play a major role in recruiting leukocytes to sites of inflammation. This is accomplished, at least in part, by up‐regulation of cell surface adhesion molecules, including VCAM‐1 and ICAM‐1, in response to cytokines. In this report, we investigated the role of the proteasome complex in mediating the interleukin (IL)‐1β induction of VCAM‐1 and ICAM‐1 gene expression in human endothelial cells. We present evidence that a proteasome inhibitor, n‐acetyl‐leucinyl‐leucinyl‐norleucinal (norLEU), as well as specific protease inhibitors, n‐tosyl‐Lys‐chloromethylketone and n‐tosyl‐Phe‐chloromethylketone, blocked IL‐1β induction of VCAM‐1 and ICAM‐1 promoter‐driven reporter gene expression in stably transfected endothelial cells. These inhibitors also blocked cytokine induced cell surface expression of VCAM‐1 and ICAM‐1 by human umbilical vein endothelial cells. As expected, the protease inhibitors blocked the activation of nuclear factor (NF)‐ϰB in response to IL‐1β stimulation. In contrast, norLEU did not prevent IL‐1β‐induced nuclear translocation of NF‐ϰB. The effects of norLEU were specific because it did not inhibit the IL‐1β induction of plasminogen activator inhibitor type 1 gene expression. This study demonstrates that inhibition of the proteolytic activity of the proteasome blocks IL‐1β induction of VCAM‐1 and ICAM‐1 gene expression in human endothelial cells.
A new Ig‐superfamily member, molluscan defence molecule (MDM) from Lymnaea stagnalis, is down‐regulated during parasitosis
Authors: Hoek Robert M. , Smit August B. , Frings Heleen , Vink Jacqueline M. , de Jong‐Brink Marijke , Geraerts Wijnand P. M. 
Published: March 2007

AbstractTo survive the attacks of the internal defence system (IDS) of their host, parasites have developed various strategies to manipulate the IDS. We present evidence that the avian schistosome parasite Trichobilharzia ocellata affects gene expression in the granular cells, a cell type of the IDS of the intermediate host, the mollusc Lymnaea stagnalis. From a differential screening, a clone was isolated encoding a protein named molluscan defence molecule (MDM), which encompasses five C2‐like immunoglobulin (Ig) domains. The protein shares a domain organization and high amino acid sequence identity with hemolin, an Ig‐family member of the insect IDS. Interestingly, both MDM and hemolin have highest sequence identity with neural cell adhesion molecules, but lack the typical fibronectin repeats and motifs for membrane anchors. We find that the expression of the MDM gene is gradually down‐regulated during the course of parasitosis to ∼21% compared to the non‐parasitized level, 8 weeks post‐infection. Based on our findings, we suggest that MDM is involved in the proper functioning of the Lymnaea IDS, and that down‐regulation of MDM is part of the parasite‐induced disabling of non‐self recognition.
Non‐obese diabetic mice hemizygous at the T cell receptor α locus are susceptible to diabetes and sialitis
Authors: Elliott James I. , Altmann Daniel M. 
Published: March 2007

AbstractTo test the hypothesis that T cells carrying two T cell receptor (TCR)α chains play a role in autoimmunity, we backcrossed the non‐obese diabetic (NOD) strain with one carrying a TCRα gene disrupted by homologous recombination. Mice carrying one copy of the disrupted gene are incapable of generating T cells carrying two cell surface TCRα chains. Our early results suggested that either dual TCRα T cells play a role in insulin‐dependent diabetes mellitus (IDDM) induction in NOD mice or that a locus co‐segregating with the disrupted TCRα locus protected mice from diabetes induction. From the analysis both of mice in which the region co‐segregating with the disrupted TCRα locus is minimized and of the F1 offspring of NOD mice with the 129 strain (TCRα hemizygous mice), the apparent protective effect of the absence of dual TCRα T cells is lost; thus, such cells do not appear to play a critical role in autoimmune disease in NOD mice.
Activity of neutral endopeptidase and aminopeptidase N in mouse thymic stromal cells which bind double‐positive thymocytes
Authors: Small Myra , Kaiser Meirav , Tse William , Heimfeld Shelly , Blumberg Shmaryahu 
Published: March 2007

AbstractThe activity of two peptidases was determined in immortalized lines of thymic stromal cells. A line of total stromal cells (T‐TG‐St) was grown from transgenic mouse expressing temperature‐sensitive SV40T antigen under the control of the regulatory elements of the mouse major histocompatibility complex class I gene. From these cells we isolated a subset (DP‐TG‐St) that binds thymocytes which are mainly CD4+8+. We also assayed a clone of fetal thymic epithelial cells (BA/10) that binds CD4+8+ thymocytes. Both lines of double‐positive cell‐binding stroma exhibited strong activity of two peptidases, neutral endopepti dase (NEP; EC 3.4.24.11) and aminopeptidase N (APN; EC 3.4.11.2). In contrast, the activity of both enzymes was very low in the total thymic stromal line. Use of specific inhibitors confirmed that these two enzymes were responsible for the activity observed but also suggested the presence of additional unidentified aminopeptidase(s) in the same stromal cells. The high activity of the two peptidases on stromal cells that bind thymocytes at the double‐positive stage raises the possibility that they might contribute to the microenvironment of the developing thymocytes.
Dissection of lymphocyte function‐associated antigen 1‐dependent adhesion and signal transduction in human natural killer cells shown by the use of cholera or pertussis toxin
Authors: Poggi Alessandro , Spada Franca , Costa Paola , Tomasello Elena , Revello Valentino , Pella Nicoletta , Zocchi Maria Raffaella , Moretta Lorenzo 
Published: March 2007

AbstractThe effect of the guanosine triphosphate‐binding protein (G‐protein) inhibitors cholera toxin (Ctx) and pertussis toxin (Ptx) has been analyzed on lymphocyte function‐associated antigen 1 (LFA‐1)‐dependent adhesion and signal transduction in human natural killer (NK) cells. Ctx, but not Ptx, inhibited the LFA‐1‐dependent adhesion of NK cells to tumor target cells which constitutively express the intercellular cell adhesion molecule‐1 (ICAM‐1) and to NIH/3T3 mouse fibroblasts stably transfected with human ICAM‐1. This effect was detectable only by the use of the entire Ctx but not of the Ctx B subunit. In addition, Ctx could inhibit both NK cell binding and spreading to purified ICAM‐1 protein. NK cell treatment with Ctx modified neither the surface expression of LFA‐1 nor its Mg2+ binding site. These findings, together with the absence of any detectable effect of Ctx on the constitutive phosphorylation of LFA‐1α, suggests that this toxin modifies the avidity of LFA‐1 for ICAM‐1 by acting on LFA‐1‐cytoskeletal protein association. Unlike Ctx, Ptx did not affect NK cell adhesion. The effects of Ctx and Ptx are unlikely to depend on intracellular levels of cyclic adenosine 3′,5′‐monophosphate (cAMP), since a strong increase of cAMP was induced by both toxins. Moreover, this was confirmed by the observation that the LFA‐1‐dependent adhesion was not inhibited by the adenylate cyclase activator forskolin (FSK), the phosphodiesterase inhibitor isobutyl‐1‐methylxantine (IBMX), or both, which increase intracellular cAMP levels. Unlike the differential effect on cell adhesion, both the intracellular calcium [Ca2+]i increase and phosphoinositide breakdown mediated via LFA‐1 were consistently inhibited in a dose‐dependent manner by both Ctx and Ptx. Also in this case, the inhibitory effect did not depend on an increase of intracellular cAMP as indicated by NK cell treatment with FSK, IBMX, or both. Further evidence of the involvement of G‐proteins in LFA‐1‐mediated signal transduction was the inhibitory effect of the GDP analog guanosine‐5′‐O‐2‐thiodiphosphate (GDPßS) on LFA‐1‐mediated calcium mobilization. Taken together, our data provide evidence that the LFA‐1‐mediated NK cell adhesion and signal transduction are partially independent phenomena which may be regulated by different G‐proteins.
A Vβ4‐specific superantigen encoded by a new exogenous mouse mammary tumor virus
Authors: Maillard Ivan , Erny Katrina , Acha‐Orbea Hans , Diggelmann Heidi 
Published: March 2007

AbstractThe superantigen (SAg) expressed by mouse mammary tumor virus (MMTV) has been shown to play an essential role in the course of the viral life cycle. In the present study, we describe a Vβ4‐specific SAg encoded by a new exogenous MMTV carried by the SIM mouse strain. This is the first report of a viral or bacterial SAg reacting with mouse Vβ4+ T cells. Injection of MMTV(SIM) into adult BALB/c mice leads to a rapid and strong stimulation of Vβ4+ CD4+ T cells, followed by a slow deletion of these cells. Neonatal exposure to the virus also leads to a progressive deletion of Vβ4+ T cells. In contrast to other strong MMTV SAg, this new SAg requires the presence of major histocompatibility complex class II I‐E molecules to be presented efficiently to T cells. Sequence analysis revealed a new predicted amino acid sequence in the C‐terminal polymorphic region of this SAg. Furthermore, sequence comparisons to the most closely related SAg with different Vβ specificities hint at the specific residues involved in the interaction with the T cell receptor.