bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD9, CD63, CD81, and CD82 are components of a surface tetraspan network connected to HLA‐DR and VLA integrins
Authors: Rubinstein Eric , Le Naour François , Lagaudrière‐Gesbert Cécile , Billard Martine , Conjeaud Hélène , Boucheix Claude 
Published: March 2007

AbstractCD9, CD63, CD81, and CD82 are glycoproteins of unknown function which belong to the tetraspan superfamily. These molecules have short cytoplasmic sequences, four transmembrane domains and two unequal extracellular regions. Here, we show that these molecules are associated with each other on cell surface and with other glycoproteins such as very late antigen (VLA) integrins and HLA‐DR antigens. Moreover, the VLA integrins and HLA‐DR antigens were also found to be associated. The interactions of these molecules were analyzed by transfection experiments. It is demonstrated that overexpression of CD9 antigen in Raji cells leads to a lower efficiency of precipitation of CD81 and CD82, suggesting a direct interaction between these molecules. In these cells, the coprecipitation of CD81 and CD82 was not modified, suggesting that these tetraspans did not compete for association. However, in COS‐7 cells, transfection of both CD81 and CD82 led to a marked reduction of the number of CD9/CD81 or CD9/CD82 complexes compared to single‐transfected cells, and this was associated with the appearance of CD81/CD82 complexes. Therefore, in this cellular system, CD9 competes with CD81 and CD82 for association with the other tetraspan proteins. Finally, the tetraspans do not compete for the association with integrins or HLA‐DR. Indeed, when CD9 was expressed in Raji cells, it was incorporated into the pre‐existing complexes of these molecules with CD81 and CD82. These data suggest the existence of a tetraspan network which, by connecting several molecules, may organize the positioning of cell surface proteins and play a role in signal transduction, cell adhesion, and motility.
CD4+CD8− thymocytes that express L‐selectin protect rats from diabetes upon adoptive transfer
Authors: Seddon Ben , Saoudi Abdelhadi , Nicholson Martin , Mason Don 
Published: March 2007

AbstractPrevious studies have shown that insulin‐dependent diabetes can be induced in normal PVG.RT1u rats by a protocol of adult thymectomy and irradiation. The injection of CD4+ T cells from non‐irradiated syngeneic donors prevents the onset of disease in approximately 50 % of pre‐diabetic recipients but all rats are protected if a particular subset of CD4+ cells is transferred. These protective cells express TCRαβ and have a memory phenotype, being CD45RClow RT6+. Further studies have demonstrated that the transfer of CD4+CD8− thymocytes, like that of unfractionated CD4+ peripheral T cells, also protects approximately half of recipients from diabetes suggesting that, as with the peripheral T cells, a functional heterogeneity may exist amongst CD4+CD8− thymocytes. In this study, we show that L‐selectin is expressed by 50–60 % of all CD4+CD8− thymocytes from 6‐week‐old rats. Adoptive transfer of these populations into thymectomized and irradiated rats revealed that the protection from diabetes observed by CD4+CD8− thymocytes was mediated almost entirely by the L‐selectin+ subset. Cells with this phenotype were also able to mediate both humoral and cell mediated responses, providing primed B cells with help for secondary antibody responses and mediating local graft‐versus‐host reactions. L‐selectin− CD4+CD8− thymocytes failed to mediate these responses. These data indicate that CD4+CD8− thymocytes must mature to the stage of L‐selectin expression, before they can mediate normal T cell function. The implications of these results are discussed with respect to the possible role of murine NK1.1+ thymocytes in the control of autoimmunity.
Vascular cell adhesion molecule‐1 expression by hematopoiesis‐supporting stromal cells is not essential for lymphoid or myeloid differentiation in vivo or in vitro
Authors: Friedrich Christof , Cybulsky Myron I. , Gutierrez‐Ramos Jose‐Carlos 
Published: March 2007

AbstractBinding of myeloid and lymphoid precursors to stromal cells in bone marrow has been suggested to be mediated through α4 integrins (α4) and vascular cell adhesion molecule‐1 (VCAM‐1) expressed on hematopoietic progenitors and stromal cells, respectively. It has not been shown, however, how essential the VCAM‐1/α4 interaction is for hematopoiesis in vivo and whether or not other adhesion pathways can provide similar functional binding between stromal cells and hematopoietic progenitors. We addressed this issue by analyzing myeloid and lymphoid differentiation in vivo in mice with VCAM‐1‐null or ‐hypomorphic mutations and in vitro in long‐term hematopoietic cultures with stromal cell clones from wild‐type mice, which express or do not express VCAM‐1. Mice bearing VCAM‐1 mutations had no gross hematopoietic insufficiencies in the myeloid or lymphoid compartments and the distribution of myeloid progenitors between bone marrow and periphery was normal. In Dexter type long‐term bone marrow cultures from mutant mice, the formation of supportive stromal cell layers and myeloid proliferation and differentiation were not affected by the absence of VCAM‐1. Long‐term maintenance and proliferation of clonable pre‐B cells, cobblestone formation and differentiation to IgM‐secreting, mature B cells was equally possible on VCAM‐1+ and VCAM‐1− stromal cell clones. We conclude from our data that VCAM‐1 is not essential for the functional interaction between hematopoietic progenitors and stromal cells required for myeloid and B‐lymphoid development in vivo or in vitro.
‘Empty’ Ld molecules capture peptides from endocytosed hepatitis B surface antigen particles for major histocompatibility complex class I‐restricted presentation
Authors: Schirmbeck Reinhold , Reimann Jörg 
Published: March 2007

AbstractPeptides recognized by CD8+ cytotoxic T lymphocytes in the context of major histocompatibility complex (MHC) class I molecules are usually derived from endogenous proteins synthesized within the cell. Exogenous 22‐nm hepatitis B surface antigen (HBsAg) particles are taken up by many cells, and are processed in a novel peptide‐transporter‐independent, endosomal or lysosomal pathway for class I (Ld)‐restricted epitope presentation. Here, we present evidence that ‘empty’ Ld molecules derived from the cell surface are involved in presenting antigenic peptides from endocytosed HBsAg particles. Intracellular assembly of presentation‐competent, trimeric Ld molecules required endocytosis of the exogenous antigen and ‘empty’m Ld molecules. These data assign a functional role to surface‐associated, ‘empty’ MHC class I molecules.
Differential interaction of the CD2 extracellular and intracellular domains with the tyrosine phosphatase CD45 and the ζ chain of the TCR/CD3/ζ complex
Authors: Verhagen Anne M. , Schraven Burkhart , Wild Martin , Wallich Reinhard , Meuer Stefan C. 
Published: March 2007

AbstractT cell activation via CD2 requires interaction of CD2 with several signaling molecules. To investigate the structural requirements for an association of CD2 with the tyrosine phosphatase CD45 and the ζ chain of the T cell receptor (TCR)/CD3/ζ complex, we have expressed in mouse EL4 T cells a series of human CD2 chimeric and mutant proteins. Chimeric proteins in which the CD2 transmembrane and/or cytoplasmic domains were deleted or exchanged with analogous regions of CD4, CD28 or CD58 retained association with high levels of murine CD45 phosphatase activity, suggesting that the CD2 extracellular domain largely controls interaction with CD45. To a lesser extent, the cytoplasmic domain of CD2 was also shown to interact with CD45, as demonstrated by an increase in co‐immunoprecipitated phosphatase activity observed following replacement of the CD58 cytoplasmic domain with that of CD2. In contrast, the cytoplasmic domain of CD2 was found to be responsible for the majority of CD2 interaction with the ζ chain of the TCR/CD3/ζ complex. Deletion of the CD2 cytoplasmic domain, excluding the first three amino acids, removed virtually all CD2 associated ζ chain and approximately sevenfold higher levels of ζ chain were found in association with a CD58/58/2 chimera than with control human CD58 wild type. This study suggests that the CD2 extracellular and intracellular domains are differentially involved in regulating T cell activation through interaction with the tyrosine phosphatase CD45 and the ζ chain of the TCR/CD3/ζ complex.
Inhibition of experimental autoimmune myasthenia gravis by major histocompatibility complex class II competitor peptides results not only in a suppressed but also in an altered immune response
Authors: Wauben Marca H. M. , Hoedemaekers Astrid C. W. E. , Graus Yvo M. F. , Wagenaar Josee P. A. , van Eden Willem , De Baets Marc H. 
Published: March 2007

AbstractTo assess the capacity of major histocompatibility complex (MHC) class II‐binding competitor peptides in inhibiting antibody‐mediated disease processes, we studied experimental autoimmune myasthenia gravis in Lewis rats. Experimental autoimmune myasthenia gravis, a disease model mediated by T cell‐dependent autoantibodies against acetylcholine receptors, was induced by immunization with Torpedo californica acetylcholine receptor emulsified in complete Freund's adjuvant. The immunodominant acetylcholine receptor T cell epitope was recognized by T cells in the context of MHC class II RT1.BL. The disease inhibitory capacity of RT1.BL‐binding peptides not related to the acetylcholine receptor was determined upon co‐immunization with Torpedo acetylcholine receptor. Co‐immunization of peptide OVA323–339, a strong RT1.BL‐binding competitor peptide, resulted in complete disease inhibition. Although, the priming of the anti‐acetylcholine receptor T cell response was not fully inhibited, the kinetics of the response was changed. Moreover, besides a drastic reduction of the anti‐Torpedo acetylcholine receptor antibody titers, a shift in isotype distribution was found. These findings indicate that antibody‐mediated autoimmune processes can be suppressed by MHC class II competitor peptides. Furthermore, the administration of such peptides in vivo not only passively inhibits T cell activation, but also functionally alters the immune response.
Interleukin‐12 activates human γδ T cells: synergistic effect of tumor necrosis factor‐α
Authors: Ueta Chisato , Kawasumi Hiromi , Fujiwara Hiroshi , Miyagawa Toshi , Kida Hiroshi , Ohmoto Yasukazu , Kishimoto Susumu , Tsuyuguchi Izuo 
Published: March 2007

Abstractγδ T cell populations are known to expand in response to intracellular bacterial infectious agents regardless of previous priming. We have shown previously that soluble factor(s) produced by Mycobacterium‐stimulated monocytes activate cord blood γδ T cells to proliferate. In this study, we investigated whether cytokines produced by monocytes are responsible for γδ T cell activation in vitro: interleukin (IL)‐1β, IL‐6, IL‐8, IL‐12, tumor necrosis factor (TNF)‐α and granulocyte/macrophage colony‐stimulating factor were examined. Recombinant human IL‐12 stimulated γδ T cells, but not αβ T cells in peripheral blood mononuclear cells, to express CD25 on their surfaces, and to expand in number in vitro. IL‐12‐primed γδ T cell numbers increased to a greater extent in the culture to which exogenous IL‐2 (5 U/ml) was added. Anti‐TNF‐α monoclonal antibody inhibited IL‐12‐induced up‐regulation of CD25 on γδ T cells, suggesting that endogenous TNF‐α may play a role in IL‐12‐induced activation of γδ T cells. Recombinant TNF‐α synergistically augmented IL‐12‐induced activation of γδ T cells. Furthermore, IL‐12 up‐regulated TNF receptors on γδ T cells in vitro: TNF‐α binding to its receptor induced CD25 expression on the γδ T cells in an autocrine or paracrine fashion, or perhaps both. It also became evident that both IL‐12 and TNF‐α were produced by mycobacterial lysate‐stimulated monocytes. Taken together, these results suggest that upon confrontation with mycobacterial organisms, γδ T cells can be quickly and antigen‐nonspecifically activated by soluble factors including IL‐12 and TNF‐α, both of which are produced by mononuclear phagocytes in response to mycobacterial organisms.
Characterization of the expression and gene promoter of CD22 in murine B cells
Authors: Andersson Kristin Brevik , Draves Kevin E. , Magaletti Dario M. , Fujioka Sean , Holmes Kevin L. , Law Che‐Leung , Clark Edward A. 
Published: March 2007

AbstractCD22 is a B cell‐restricted surface molecule which may play an important role in interactions between B cells and other cells and in regulating signals through the B cell receptor (BCR) complex. Here we have examined whether the mouse is a suitable in vivo model for studying CD22 functions. In primary and secondary lymphoid organs of adult mice CD22 is on all mature B cells, including resting IgM+IgD+ B cells, IgG+ HSAlo memory B cells, syndecan+ plasma cells and CD5+ B cells, but it is not on immature IgM+IgD− B cells. Biochemical analysis revealed that murine CD22 is associated with the IgM receptor in some, but not all, CD22+ B leukemic and lymphoma cell lines; as with human CD22, murine CD22 is rapidly phosphorylated on tyrosine after ligation of the BCR. In the CD22− murine pro‐B cell line, FEMCL, CD22 expression was inducible by treatment with phorbol 12‐myristate 13‐acetate. A genomic fragment of the cd22b allele containing 1.3 kb 5′ of exon 1 was sequenced in order to identify potential DNA regulatory elements in the CD22 promoter region. Consensus sequences for transcription factor binding sites including PU.1, AP‐1, AP‐2, C/EBP and SP‐1 were present, but no classical TATA elements or initiator motifs were evident at relevant positions. The 1.3‐kb promoter fragment 5′ of exon 1 was sufficient for directing basal promoter activity in B and T cells. There was no significant sequence similarity between the murine and human cd22 gene promoters, although both contain repetitive elements and Sp‐1 and AP1 binding sites. Thus, murine CD22 shares a number of features with human CD22 and the mouse provides a suitable model system for elucidating the function of CD22 in vivo.
Split activity of interleukin‐10 on antigen capture and antigen presentation by human dendritic cells: Definition of a maturative step
Authors: Morel Anne‐Sophie , Quaratino Sonia , Douek Daniel Cesar , Londei Marco 
Published: March 2007

AbstractHuman CD1+ CD14‐ dendritic cells (DC) can be derived from CD14+ monocytes using granulocyte/monocyte colony‐stimulating factor and interleukin (IL)‐4. We have previously shown that IL‐10 pre‐treatment of such DC significantly inhibited their antigen‐presenting capacity to CD4+ T cell clones. In this study, we further analyze how IL‐10 influences antigen presentation. We first investigated whether IL‐10 could alter the early stage of antigen presentation, the capture of antigen. This can be mediated by mannose receptor (MR)‐mediated endocytosis and by fluid‐phase uptake through macropinocytosis. IL‐10‐treated DC showed an enhancement of both mechanisms of antigen capture, as indicated by the increase of fluorescein isothiocyanate‐dextran uptake through MR and lucifer yellow uptake. However, IL‐10‐treated DC, irradiated or glutaraldehyde‐fixed, were less efficient than untreated DC in stimulating mixed leukocyte reaction as well as in inducing the activation of peptide‐specific T cell clones, indicating that IL‐10 achieves its effects mainly by modifying the cell surface phenotype of DC. HLA class I and II, as well as intercellular adhesion molecule (ICAM)‐1, lymphocyte function‐associated antigen‐3, B7‐1, B7‐2 and ICAM‐3 expression were either significantly increased or essentially unchanged, and the ability to bind the epitope recognized by the T cell clones was also unaffected regardless of IL‐10 treatment. Our study also indicates that as‐yet unidentified accessory molecules may play an essential role in T cell activation. Thus, the IL‐10‐treated DC possess an increased capacity to capture antigen, with a concomitant decreased stimulatory activity. Our study suggests that IL‐10‐treated DC have the characteristics of highly immature DC (high capture ability, low stimulatory potency) and may represent an early maturative step of human DC of monocytic origin.
CD21 augments antigen presentation in immune individuals
Authors: Boackle Susan A. , Holers V. Michael , Karp David R. 
Published: March 2007

AbstractCD21 (complement receptor 2, CR2) binds the C3 degradation products, iC3b and C3d, which are covalently linked to antigen or immune complexes in the process of complement activation. The ability of antigen‐nonspecific B cells to present immune complexes containing high titers of acquired antibodies was tested. Influenza virus was incubated with serum from immune donors to create complement‐containing complexes. These bound specifically to CD21 on transfected fibroblasts and B cell lines, as measured by microcytofluorimetry. Binding of immune complexes was ablated by inactivation of serum complement. In addition, the immunoglobulin in immune human serum blocked influenza binding to cells in the absence of complement, implying a minimal role for immunoglobulin‐Fc receptor interactions in this system. Significant immune complex binding required a threshold level of CD21 expression, suggesting that only those cells with the highest levels of CD21 are likely to participate in the processing of macromolecular antigens. B cells pulsed with complement‐influenza complexes elicited an augmented response from a panel of influenza‐specific, class II‐restricted T cell clones, as compared with those which had bound immunoglobulin‐influenza complexes lacking complement. This enhanced response did not require CD35. In addition, B cell lines expressing higher levels of CD21 were more efficient in processing antigen than those with lower levels. These findings suggest that presentation of antigen by B cells in immune individuals is dependent on the binding of complement‐antigen immune complexes to CD21.
Identification and analysis of the chicken CD3ε gene
Authors: Göbel Thomas W. F. , Fluri Monika 
Published: March 2007

AbstractThe chicken T cell receptor CD3ε gene was isolated using a degenerate polymerase chain reaction. The 1883 bp long cDNA encoded a transmembrane protein of 16.9 kDa lacking N‐linked glycosylation sites. Comparison of the chicken and mammalian CD3ε proteins revealed low homology in the extracellular domain with clusters of similarities located around the N‐terminal cysteine residue and proximal to the transmembrane region. The high conservation of the cytoplasmic domain included motifs important for signal transduction. The alignment of all CD3γ, CD3δ and CD3ε proteins allowed the identification of highly conserved residues and motifs. Southern blot analysis indicated the presence of a single copy CD3ε gene. The expression of the CD3ε transcript was limited to T cells and natural killer cells. A recessive mutation of the CD3ε gene in the CB chicken strain enabled the mapping of the epitope recognized by the CT3 monoclonal antibody. This analysis of the first non‐mammalian CD3ε gene provides novel information about evolutionary conserved structural features and its expression in natural killer cells.
Genetic defect in T lymphocyte‐specific homing into peripheral lymph nodes
Authors: Nakano Hideki , Tamura Toshiki , Yoshimoto Takayuki , Yagita Hideo , Miyasaka Masayuki , Butcher Eugene C. , Nariuchi Hideo , Kakiuchi Terutaka , Matsuzawa Akio 
Published: March 2007

AbstractLymphocytes circulating in the bloodstream home into lymph nodes (LN). T cells predominate in peripheral LN (PLN) and B cells in spleen or mucosal tissue, e.g. Peyer's patches (PP). DDD/1 mice are unique in marked paucity of LN cells, especially T cells. T cell frequency in PLN was 20–40% in this strain, compared to 60–80% in others. Immunohistochemistry confirmed the low density of T cells in the subcortical area but normal colonization of B cells in cortical area in PLN of DDD/1. In contrast, the T cell content of peripheral blood and spleen was higher in DDD/1 but that in PP was not significantly different compared to other strains. It was thus concluded that this abnormality in DDD/1 results from a homing defect of T cells into PLN but not from lymphopenia. Genetical analysis showed that the defect in T cell‐specific homing was regulated by a single autosomal recessive gene, tentatively designated plt (paucity of lymph node T cells). Reciprocal bone marrow transplantation indicated that the plt phenotype may arise from some defect in PLN stroma but not in lymphocytes. An in vivo homing assay using fluorescence‐labeled lymphocytes demonstrated that the homing defect was specific for T cells but not for B cells. A Stamper‐Woodruff assay revealed that the binding between lymphocytes and PLN high endothelial venules was normal and that L‐selectin and its ligand, peripheral node vascular addressin (PNAd), were expressed and functioned normally in DDD/1. These results taken together indicate that the T cell‐specific homing into PLN is disturbed at a post‐adhesion stage in DDD/1. The product of the plt locus may play a pivotal role at this stage.
Synergy between an antibody and CD8+ cells in eliminating an established tumor
Authors: Vasović Ljiljana V. , Dyall Ruben , Clynes Raphael A. , Ravetch Jeffrey V. , Nikolić‐Žugić Janko 
Published: March 2007

AbstractWe investigated the effector mechanisms operating during the rejection of a transplantable solid lymphoma E.G7 (H‐2b) which expresses the gene encoding chicken ovalbumin (OVA). Anti‐OVA cytotoxic T lymphocytes (CTL) completely and specifically protected animals from the onset of, but could not eradicate established, E.G7 tumors. The growth of the same lymphoma was also effectively prevented by the antibody GK1.5, whose target molecule, CD4, was expressed on E.G7 cells in vivo. Furthermore, GK1.5 was able to eradicate established solid E.G7 tumors. GK1.5‐mediated tumor elimination was due to its antitumor activity, and not to the elimination of regulatory CD4+ cells, based on unimpaired tumor growth in the absence of GK1.5 in animals that genetically lack CD4 T cells. In vitro, GK1.5 did not kill tumor cells: complement activation or apoptosis induction were not evident. In vivo, GK1.5‐mediated tumor regression did not depend on natural killer cells, but it absolutely required CD8+ cells and intact Fcγ receptor. We conclude that, in the E.G7 model, the collaboration of antibody and CTL immunity was crucial for the successful immunotherapy of established tumors. The mechanism of this collaboration is discussed.