bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autoimmune syndrome after induction of neonatal tolerance to I‐E antigens
Authors: Gonzalez Antonio L. , Conde Carmen , Revilla Conchi , Ramos Angeles , Renedo Blanca , Merino Jesús 
Published: March 2007

AbstractNeonatal injection of semiallogeneic spleen cells induces a state of specific tolerance to the parental alloantigens, but also the development of an autoimmune syndrome known as host‐versus‐graft disease (HVGD). The autoimmune features are a consequence of the allogeneic cooperation between persisting alloreactive host T helper type 2 (TH2) cells and donor semiallogeneic B cells. It has been established that I‐A alloantigens play a central role in the triggering of this HVGD. Here it was investigated if I‐E antigens, which have shown functional differences, regarding autoimmunity and alloreactivity, with respect to I‐A antigens, are also able to trigger this autoimmune syndrome. The injection of spleen cells from [B10.A(4R) X B10.A(2R)]F1 (I‐E+) hybrid mice into newborn B10.A(4R) (I‐E−) mice was accompanied by the establishment of chimerism and also by the development of a characteristic, but moderated, HVGD. The weak intensity of this HVGD is likely due to the moderation of the alloreactive responses induced against I‐E molecules. Moreover, the marked increase in the levels of IgE and in the titers of anti‐DNA IgGl antibodies strongly suggest that alloreactive TH2 cells play also a main role in the autoimmune syndrome following tolerization to I‐E antigens. Therefore, it is concluded that the I‐E and I‐A isotypes are functionally similar with respect to the allogeneic cellular interactions that account for the HVGD.
A mouse aminopeptidase N is a marker for antigen‐presenting cells and appears to be co‐expressed with major histocompatibility complex class II molecules
Authors: Hansen Anette Stryhn , Norén Ove , Sjöström Hans , Werdelin Ole 
Published: March 2007

AbstractTo analyze the expression of mouse aminopeptidase N (APN) on the cells of the immune system a panel of rat monoclonal antibodies against mouse intestinal APN was generated. These antibodies were used to affinity purify functional mouse APN from both intestine and kidney, and by flow cytometry to examine the APN expression of the cells of the mouse immune system. An APN closely related, perhaps identical, to the intestinal APN was expressed on a subpopulation of spleen cells and stimulated peritoneal exudate cells, primarily representing antigen‐presenting cells, such as B cells, macrophages, dendritic cells, and veiled cells. In contrast this APN expression could not be detected on thymocytes or spleen T cells. As a corollary, APN was expressed on monocyte, macrophage, and B lymphoma cell lines, but not on T hybridoma or thymoma cell lines. The expression of APN showed a striking correlation with the MHC class II expression in all the cell populations studied. This apparent co‐expression suggests a role for APN in antigen processing.
Autoimmune gld mutation uncouples suicide and cytokine/proliferation pathways in activated, mature T cells
Authors: Russell John H. , Wang Ruduan 
Published: March 2007

AbstractAntigen receptor‐directed suicide plays an important role in the elimination of potentially autoaggressive immature T cells during thymic differentiation. Here we demonstrate evidence for a second pathway of receptor‐directed suicide in mature T cells that is missing in a mutant strain (gld) of mice with an “autoimmune” lymphoproliferative syndrome. The defect is evident within the gld activated T cell and does not require the presence of an antigen‐presenting cell for its expression. Receptor‐driven suicide is intact in immature T cells of animals with this mutation. These results support the significance of receptor‐directed suicide in the mature T cell compartment and suggest that the immune system may use three independent pathways for regulating programmed cell death in shaping and controlling the immune response.
Human CD38 is associated to distinct molecules which mediate transmembrane signaling in different lineages
Authors: Funaro Ada , De Monte Lucia B. , Dianzani Umberto , Forni Marco , Malavasi Fabio 
Published: March 2007

AbstractThe CD38 antigen displays restricted functional associations with surface molecules involved in immune system and complement. Capping of the CD38 molecule in normal or neoplastic T cells is followed by rapid and specific co‐modulation of the CD3‐Tcell receptor (TcR) complex. In normal and tumor cells of B lineage, CD38 was found to be also associated with surface Ig (sIg) and with the complement receptor 2 (CR2)/CD19 complex. The CD38 molecule expressed by purified natural killer cells displayed an association with the low affinity IgG Fc receptor (FcγRIII) CD16. These observations suggest that specialized areas in the plasma membrane contain co‐modulating structures, including different receptors involved in the transduction of extracellular signals. We propose a model whereby TcR, CR2 and CD16 are ligand binding structures in their respective lineages, while CD38 is a molecule involved in the intracellular transduction of the signals.
Long‐term thymic reconstitution by peripheral CD4 and CD8 single‐positive lymphocytes
Authors: Hilbert David M. , Holmes Kevin L. , Anderson Arthur O. , Rudikoff Stuart 
Published: March 2007

AbstractSignificant immigration of peripheral T cells into SCID thymus was observed following reconstitution with normal Peyer's patch, mesenteric lymph node or peripheral lymph node cells. Immunohistologic and flow cytometric analyses reveal that T cells from these tissues are found in the thymus for as long as 177 days and can account for up to 67% of intrathymic cells. The returning cells express the CD3/Tcell receptor α/β complex, indicative of mature cells, and are equally divided among helper (CD4+ CD8 ) and cytotoxic (CD4−/CD8+) phenotypes. The immigration of peripheral T cells is not accompanied by the appearance of immature, double‐positive (CD4+CD8+) thymocytes as seen in similar reconstitutions using bone marrow. Taken together, these results suggest that peripheral T cells from a variety of lymphoid organs may regularly re‐enter the thymus and, thus, possibly play a role in normal thymic development.
The monoclonal antibody CZ‐1 identifies a mouse CD45‐associated epitope expressed on interleukin‐2‐responsive cells
Authors: Brutkiewicz Randy R. , O'Donnell Carey L. , Maciaszek Joseph W. , Welsh Raymond M. , Vargas‐Cortes Mauricio 
Published: March 2007

AbstractWe have previously described a monoclonal antibody (mAb), CZ‐1, which reacts with an epitope expressed on most peripheral basophils, natural killer cells, B cells, and CD8+ T cells, but not with most thymocytes or peripheral CD4+ T cells. Here we show that mAb CZ‐1 defines a sialic acid‐dependent epitope associated with a subpopulation of CD45 molecules. This conclusion is based on the ability to block binding of mAb CZ‐1 by sialic acid, neuramin‐lactose, neuraminidase, and mAb to CD45RB, and by expression of the epitope on transfected W2 cells expressing exon B of CD45. The results suggest that the CZ‐1 epitope is a post‐translational modification expressed on a subpopulation of the CD45 molecules also expressing the B exon. Expression of the CZ‐1 epitope was required for freshly isolated lymphocytes to respond to interleukin‐2 (IL‐2). Depletion of CZ‐1+ cells by C or by cell sorting of thymocytes or splenocytes eliminated the IL‐2 responsive cells. The subpopulations of thymocytes and CD4+ splenocytes responding to IL‐2 were exclusively within the small CZ‐1+ subpopulation. mAb CZ‐1 was also used to subdivide CD45+ and CD45RB+ splenocytes into IL‐2‐responsive and ‐nonresponsive subpopulations. The CZ‐1 epitope was also expressed on virtually all lymphokine‐activated killer cell precursors. These data, thus, indicate that cells responsive to IL‐2 express this sialated modification of CD45.
Interferon‐γ regulation of C4 gene expression in cultured human glomerular epithelial cells
Authors: Zhou Wuding , Duncan Campbell R. , Martin John , Sacks Steven H. 
Published: March 2007

AbstractThe fourth component of human complement is mainly produced in liver, but extrahepatic gene expression has been reported in human renal tissue and other tissues, and is thought to contribute to the inflammatory reaction in local tissue. To identify the cellular origin of C4 synthesis in human kidney, we studied C4 gene expression and regulation by interferon‐γ (IFN‐γ) and C4 protein biosynthesis in isolated glomerular epithelial cells. cDNA/polymerase chain reaction analysis showed that C4 transcripts are present in glomerular epithelial cells (GEC), and that gene expression is up‐regulated by IFN‐γ. Metabolic labeling studies showed that GEC synthesize and secrete C4 as three polypeptide chains of ∼ 90, 70, and 30 kDa, which correspond to the bands produced by hepatoma cells. These results suggest that the fourth component of complement is produced by GEC. The GEC has an important role in the maintenance of glomerular barrier function, which is lost in a number of complement‐dependent conditions; glomerular epithelial synthesis of C4 could have a bearing on the possible physiological or pathological roles of complement under different circumstances.
Association of the p56lck protein tyrosine kinase with the FCγRIIIA/CD16 complex in human natural killer cells
Authors: Catherine Cone J. , Lu Yiling , Trevillyan James M. , Bjorndahl Jay M. , Phillips Catherine A. 
Published: March 2007

AbstractThe multimeric FcγRIIIA (CD16) complex is expressed on the surface of natural killer (NK) cells and is composed of a 50–70‐kDa transmembrane glycoprotein Fcγ receptor (CD16), the T cell receptor (TCR)‐ζ chain, and the FcεRIγ chain. Cross‐linking FcγRIIIA initiates the rapid tyrosine phosphorylation of multiple substrates including the ζ, subunit and causes subsequent cell activation and antibody‐dependent cellular cytotoxicity (ADCC). The subunits of the FcγRIIIA complex lack intrinsic protein tyrosine kinase (PTK) activity, suggesting that receptor‐induced tyrosine phosphorylation events are mediated by a nonreceptor PTK. We report here that the human FcγRIIIA is complexed with p56lck, a src‐family PTK previously found associated with the CD4 and CD8 receptors on T cells. Upon engagement of the CD16 receptor, p56lck is rapidly (within 30 s) and transiently phosphorylated on tyrosine residues. Several FcγRIIIA‐associated proteins are identified in immune complex kinase assays including the TCR‐ζ, subunit, a p70–90 ζ‐associated protein (ZAP), p50a (acidic) and p50b (basic), and p56lck. We demonstrate that the src‐family protein tyrosine kinase inhibitor, herbimycin A, blocks increased intracellular calcium levels and ADCC caused by CD16 cross‐linking on NK3.3 cells. Likewise cross‐linking CD16 with the protein tyrosine phosphatase CD45, abrogates CD16‐induced calcium mobilization. These data suggest that p56lck is physically associated with FcγRIIIA(CD16) and functions to mediate signaling events related to the control of NK cellular cytotoxicity.
Variable region gene selection of immunoglobulin G‐expressing B cells with specificity for a defined epitope on type II collagen
Authors: Mo John A. , Bona Constantin A. , Holmdahl Rikard 
Published: March 2007

AbstractImmunization with type II collagen (CII) induces collagen‐induced arthritis (CIA) in animals, and B cells reactive with CII are involved in the induction and manifestation of the disease. In this study, B cell hybridomas producing IgG antibodies specific for a major epitope on mouse CII (the “C1” epitope, amino acid 316–333), were isolated 11 days after immunization from draining lymph nodes in DBA/1 mice. Injection into neonatal mice of purified and biotinylated monoclonal antibodies binding the C1 epitope led to a specific binding to joint cartilage, demonstrating that the antibodies interact with native antigen in vivo. cDNA sequencing of the B cell clones revealed that they all expressed the same combination of a variable heavy chain (VH J558 family) and light chain (Vx21 family) germ‐line gene, apparently lacking somatic mutations. The presence of isotype‐switched B cells expressing a certain combination of V genes encoding antibodies that bind epitopes in vivo, indicates that this B cell population has been peripherally selected.
Migration patterns of thymus‐derived γδ T cells during chicken development
Authors: Dunon Dominique , Cooper Max D. , Imhof Beat A. 
Published: March 2007

AbstractCell transfer experiments in congenic chick strains, one of which expresses the ov antigen marker, indicate that intestinal γ δ T cells are derived from γ δ + thymocytes in embryos and newly hatched birds, and this early intestinal colonization occurs in two discrete waves. Here, we extend these studies to show that splenic colonization by γ δ T cells occurs in essentially the same way. Following the engraftment of ov+ thymic lobes in thymectomized ov− recipients, γ δ T cells migrate both to the spleen and intestine. By 1 week after hatching, a third generation of thymus‐derived γ δ T cells begins to migrate to both peripheral lymphoid organs, and this thymus‐dependent seeding process is sustained over the first weeks of life. The survival time for splenic γ δ migrants is significantly less than for the intestinal migrants. Tissue section analysis indicates that γ δ T cells enter the intestinal epithelium at all villus levels. A shift in the γ δ intraepithelial lymphocyte distribution toward the villus tip in thymectomized birds suggests the comigration of enterocytes and γ δ intraepithelial lymphocytes. However, survival kinetics of the donor γ δ population and a relatively high division rate of intestinal γ δ T cells indicate that founder thymic migrants produce relatively long‐lived clones of intestinal γ δ T cells.
Immunization against tumor and minor histocompatibility antigens by eluted cellular peptides loaded on antigen processing defective cells
Authors: Franksson Lars , Petersson Max , Kiessling Rolf , Kärre Klas 
Published: March 2007

AbstractMaterial eluted from RMA lymphoma or B6 spleen cells under acid conditions was fractionated by reverse phase high‐performance liquid chromatography, and tested for ability to restore the sensitivity to cytotoxic T lymphocytes of the processing/presentation defective mutant line RMA‐S. This allowed identification of three fractions (termed M1, M2 and M3) carrying B6 antigens recognized by cytotoxic T lymphocytes (CTL) elicited across the minor histocompatibility barrier A. BYanti‐B6 (both H‐2b) and one fraction (termed TI) carrying a tumor antigen recognized by B6 anti‐RMA CTL. By parallel runs of material from cell lysates over major histocompatibility complex class I affinity columns, the M2 and M3 antigens were defined as Kb restricted, and M1 and T1 as Db restricted. Isolated fractions loaded onto RMA‐S cells could be used to prime anti‐minor histocompatibility antigen and tumor CTL in vivo. They could also be used for in vitro restimulation of spleen cells from mice that had been primed either by antigen‐loaded RMA‐S, or by wild‐type RMA tumor cells and B6 splenocytes. The CTL generated by these methods were specific for the loading antigen, and they also recognized the antigen on the “physiological” target, i.e. RMA or B6 lymphoblasts. This system based on RMA‐S as an immunization and target antigen reporter cell may be used for dissection of complex CTL responses, e.g. in studies of clonal composition and epitope dominance, or for studies of tumors that are poor stimulators of immunity.
Post‐receptor occupancy events in leukocytes during β1 integrin‐ligand interactions
Authors: Sánchez‐Mateos Paloma , Arroyo Alicia G. , Balboa María A. , Sánchez‐Madrid Francisco 
Published: March 2007

AbstractLeukocyte adhesion to and subsequent spreading on the endothelium are the initial steps in the migration of these cells to the surrounding tissues. We have investigated the participation of different VLA heterodimers in cell spreading by using the anti‐β1 TS2/16 monoclonal antibody (mAb) which induces a conformational change of different VLA integrin receptors, enabling a high‐affinity interaction with their ligands. Both VLA‐4 and VLA‐5 fibronectin (FN), as well as VLA‐2 collagen (COL) receptors mediated cell spreading and morphological changes. The spreading of U‐937 and α4‐transfected K‐562 cells was induced in both FN and VCAM‐1, suggesting that the morphological changes may be induced by cell‐cell as well as cell‐extracellular matrix (ECM) interactions. Furthermore, the β‐regulated cell spreading on VCAM‐1 and COL took place independently of the VLA‐5 FN receptor function. The enhancing effect on cell attachment induced by anti‐β1 TS2/16 mAb was observed in the presence of different doses of cytochalasin D, whereas cell spreading was abolished. Signal transduction during β1‐stimulated integrin‐ligand interaction was also investigated. We have found the co‐localization of β1 integrins and tyrosine‐phosphorylated proteins during the spreading of U‐937 and α2‐ and α4‐transfected K‐562 cells on both ECM (FN and COL) and cellular (VCAM‐1) ligands. Kinetic studies showed that tyrosine phosphorylation was almost coincident with cellular spreading. The tyrosine phosphorylation of polypeptides of 130 kDa and 77 kDa was triggered in U‐937 cells by the interaction of FN with the VLA‐5 receptor in a high‐affinity conformation. However, no signaling was observed by inducing the high‐affinity state of receptor in the absence of appropriate ligand. These data suggest that tyrosine kinase activation is a post‐receptor occupancy event that might be critical in regulating the adhesive properties of integrins.
Divergent effects of interleukin‐10 on cytokine production by mononuclear phagocytes and endothelial cells
Authors: Sironi Marina , Muñoz Cecilia , Pollicino Teresa , Siboni Andrea , Sciacca Francesca Luisa , Bernasconi Sergio , Yecchi Annunciata , Colotta Francesco , Mantovani Alberto 
Published: March 2007

AbstractInterleukin‐10 (IL‐10), a product of T helper type 2 (TH2) cells and monocytes, inhibits cytokine production in mononuclear phagocytes. Given the similarities and interrelationship between cells of the monocyte‐macrophage lineage and endothelial cells, we examined the effects of IL‐10 on vascular endothelium. Murine IL‐10 induced low levels of IL‐6 production and amplified induction of IL‐6 by lipopolysaccharide (LPS) or IL‐1 in the murine tEND.1 endothelioma line, used for these studies because it retains properties of normal endothelium. The effect was more evident after prolonged (48–72 h) exposure to IL‐10. IL‐10 had similar activity on other endothelioma lines, whereas it inhibited IL‐6 production by peritoneal macrophages. Induction and amplification of cytokine production by IL‐10 was associated with higher levels of mRNA, which were maintained longer (up to 48 h) than in controls. In addition to IL‐6, murine IL‐10 induced or amplified expression of the chemoattractant cytokines monocyte chemotactic protein‐1 (MCP‐1) and KG Human IL‐10 inhibited IL‐6 release by LPS‐stimulated human peripheral blood mononuclear cells, whereas it did not interfere with cytokine production by LPS‐ or IL‐1‐stimulated human umbilical vein endothelial cells. The selective inhibitory action of IL‐10 on mononuclear phagocytes versus endothelial cells may play a role in the pathophysiology of TH2‐directed responses.
Staphylococcal enterotoxin B up‐regulates interleukin‐2 receptor β chain expression on tonsillar B cells
Authors: Franz Annette , Bryant Annette , Farrant John 
Published: March 2007

AbstractThe superantigen staphylococcal enterotoxin B (SEB) selectively up‐regulates the interleukin‐2 receptor (IL‐2R) β chain (p70) without up‐regulating the IL‐2R a chain (CD25) on a human tonsillar B cell population depleted of T cells. This action of SEB, probably mediated by binding to major histocompatibility complex class II, renders B cells sensitive to T cell‐derived IL‐2 and is sufficient for induction of vigorous DNA synthesis with low concentrations of IL‐2. This explains one of the mechanisms by which bacterial superantigens activate large numbers of B cells and may reflect a similar mechanism operative in cognate helper T cell/B cell interactions.
Interleukin‐10 inhibits the induction of monocyte procoagulant activity by bacterial lipopolysaccharide
Authors: Pradier Oliver , Gérard Catherine , Delvaux Anne , Lybin Myriam , Abramowicz Daniel , Capel Paul , Velu Thierry , Goldman Michel 
Published: March 2007

AbstractMonocytes stimulated with bacterial lipopolysaccharide (LPS) generate a procoagulant activity (PCA) related to the induction of tissue factor (TF) expression at their surface. Since interleukin‐10 (IL‐10) was recently shown to inhibit LPS‐induced cytokine production and is currently considered as a potential therapeutic agent in septic shock, we were interested to determine its effects on LPS‐induced monocyte PCA. Peripheral blood mononuclear cells (PBMC) from healthy donors were incubated with 1 μg/ml LPS in the presence of serial dilutions of recombinant human IL‐10 and PCA was determined after 6 h in a one‐stage clotting assay. IL‐10 inhibited in a dose‐dependent manner LPS‐induced TF‐dependent PCA: a significant effect was already observed with 30 pg/ml IL‐10 while 64–97% inhibition was achieved with 120 pg/ml IL‐10. In parallel flow cytometry experiments, IL‐10 was shown to block LPS‐induced TF expression at the surface of monocytes. In order to inhibit LPS‐induced PCA, IL‐10 had to be added to PBMC at least 6 h before LPS challenge. This inhibitory effect of IL‐10 was already apparent at the TF mRNA level and was prevented by co‐incubation with cycloheximide (20 μg/ml). These data suggest that IL‐10 acts via the induction of protein(s) which might interfer with TF gene transcription or mRNA stability. We conclude that the protective effects of IL‐10 in endotoxinemia might be related not only to cytokine synthesis blockade but also to inhibition of LPS‐induced PCA.
Age‐related increase of CD45RO+ lymphocytes in physically active adults
Authors: Gabriel Holger , Schmitt Barbara , Kindermann Wilfried 
Published: March 2007

AbstractThe CD45RO phenotype of peripheral blood CD4+ and CD8+ lymphocytes were determined in physically active males (n = 171) and females (n = 70) ranging in age from 15–68 years. Direct immunofluorescence and dual color flow cytometry was performed for analysis. Absolute cell numbers (r = 0.473) and percentages of CD4+ CD45RO+ (r = 0.648) within the CD4+ population, percentage of CD8+ CD45RO+ cells within the CD8+ lymphocytes (r = 0.498) and total lymphocyte number (r = −0.242) correlated significantly (p < 0.001) with age. We conclude that the age‐related increase of CD45RO+ T cells indicates a gradual increase of activated T cells.
Triggering via the alternative CD2 pathway induces apoptosis in activated human T lymphocytes
Authors: Wesselborg Sebastian , Prüfer Ulrike , Wild Martin , Schraven Burkhard , Meuer Stefan C. , Kabelitz Dieter 
Published: March 2007

AbstractActivation of immature thymocytes or transformed (i.e. leukemic) T lymphocytes via CD3/T cell receptor (TcR) signaling can induce programmed cell death (apoptosis). Recent data indicate that anti‐CD3/TcR monoclonal antibodies (mAb) also trigger apoptosis in activated (but not resting) mature peripheral LT cells. We now report that interleukin‐2 (IL‐2) dependent human polyclonal T cell lines as well as T cell clones undergo programmed cell death when triggered via the alternative CD2‐dependent activation pathway. In the presence of exogenous IL‐2, a pair of mitogenic anti‐CD2 mAb suppressed the IL‐2‐driven proliferative response. Growth inhibition was associated with cell death and DNA fragmentation as revealed by propidium iodide staining and gel electrophoresis, respectively. Induction of apoptosis by anti‐CD2 mAb was prevented by cyclosporine A and FK 506. We conclude that programmed cell death can be initiated in activated human T cells by signaling via the CD2 pathway.