bluuebunny/crossref_metadata_2025_split huggingface dataset:
A complementarity‐determining region peptide of an anti‐desmosome autoantibody may interact with the desmosomal plaque through molecular mimicry with a cytoplasmic desmoglein 1 sequence
Authors: Gilbert Danièle , Courville Philippe , Brard Frédéric , Joly Pascal , Petit Samuel , Bernardi Elisabeth , Schoofs Alain‐René , Lauret Philippe , Tron François 
Published: March 2007

AbstractThe sera of patients with pemphigus, a group of autoimmune blistering skin diseases, contain autoantibodies directed against components of adhering junctions termed desmosomes. F12, a human monoclonal antibody derived from a pemphigus patient, recognizes an unknown polypeptide of the desmosomal and hemidesmosomal plaques. The third complementarity‐determining region of the F12 heavy chain (VH‐CDR3) was shown to share a four‐amino‐acid sequence (GSSG) with the intracellular domains of desmoglein 1 and bullous pemphigoid antigen 2 which interact with components of, respectively, the desmosomal and hemidesmosomal plaques. Computer modeling of F12 showed that the GSSG sequence protudes inside the antigen‐combining site and thus might be involved in antigen interactions. The GSSG sequence is essential to F12 function, since a peptide containing the VH‐CDR3 inhibited its binding to target antigens while VH‐CDR3 peptides with specific modifications of the GSSG sequence did not. These data allow us to hypothesize that certain autoantibodies produced during the course of an autoimmune disease can behave as adhesion molecules, through the molecular mimicry of the motif involved in protein/protein adhesion, and to propose a new self‐antigen binding mechanism for some autoantibodies.
Co‐stimulatory pathways controlling activation and peripheral tolerance of human CD4+CD28− T cells
Authors: Park Won , Weyand Cornelia M. , Schmidt Dorle , Goronzy Jörg J. 
Published: March 2007

AbstractCo‐stimulation mediated by the CD28 molecule is considered critical in the activation of CD4+ T cells. In patients with rheumatoid arthritis and infrequently in normal individuals, CD4+ T cells lacking CD28 expression are expanded and contain clonogenic populations. To analyze whether these cells are independent of co‐stimulatory requirements or whether they use co‐stimulatory signals distinct from the CD28 pathway, we have compared CD4+ CD28+ and CD4+ CD28−T cell clones isolated from rheumatoid arthritis patients. Accessory cells supported the induction of CD25 expression as well as of proliferative responses after anti‐CD3 cross‐linking and prevented the induction of anergy in CD4+ CD28− T cell clones. In contrast to CD4+CD28+ T cells, the presence of accessory cells did not enhance the secretion of interleukin (IL)‐2, interferon‐γ, or IL‐4. The co‐stimulatory signals did not involve CD28/CTLA‐4–CD80/CD86 receptor‐ligand interactions. The proliferative response of CD4+CD28− T cells could not be blocked by anti‐CD2, anti‐CD18, and anti‐CD58 antibodies, suggesting that these receptor‐ligand interactions cannot provide CD28− independent co‐stimulation. Our data suggest that CD4+CD28− T cells require co‐stimulatory signals for optimal induction of cell growth and CD25 expression as well as for the prevention of anergy. The co‐stimulatory receptor‐ligand interaction is independent of the CD28 pathway and may be involved in the oligoclonal expansion of the CD4+ CD28− T cell subset in rheumatoid arthritis.
L‐selectin is not essential for naive CD4 cell trafficking or development of primary responses in Peyer's patches
Authors: Bradley Linda M. , Malo Mary E. , Tonkonogy Susan L. , Watson Susan R. 
Published: March 2007

AbstractWe showed previously that L‐selectin‐dependent recirculation of naive CD4 cells is essential for development of primary responses in peripheral lymph nodes. Recent studies suggest that L‐selectin is also required for lymphocyte entry into gut mucosal lymphoid tissues that include Peyer's patches and mesenteric lymph nodes. Here we show that anti‐L‐selectin antibody, MEL‐14, inhibited homing of a rigorously purified, homogenous population of naive CD4 cells into both of these tissues as well as peripheral lymph nodes, directly demonstrating a role for this receptor in regulating entry into gut‐associated sites. However, in intact animals, treatment with MEL‐14 resulted in the loss of naive CD4 cells (CD45RBhi, CD44lo) from peripheral lymph nodes but not Peyer's patches, whereas mesenteric lymph nodes were intermediate in this regard. In mice primed by parenteral immunization with keyhole limpet hemocyanin (KLH), primary CD4 responses were readily detected in both Peyer's patches and mesenteric lymph nodes, and were not affected by exposure to MEL‐14. Indeed, similar frequencies of KLH‐specific CD4 cells were recovered from both of these tissues irrespective of MEL‐14 treatment. The results indicate that interactions with L‐selectin can be circumvented to allow entry of naive CD4 cells into Peyer's patches but not peripheral lymph nodes.
The mechanism of specific prolongation of class I‐mismatched skin grafts induced by retroviral gene therapy
Authors: Mayfield Robin Stanton , Hayashi Hideki , Sawada Tokihiko , Bergen Kate , Leguern Christian , Sykes Megan , Sachs David H. , Iacomini John 
Published: March 2007

AbstractIn the present study, we examine the mechanism of specific hyporesponsiveness to major histocompatibility complex (MHC) class I‐mismatched skin allografts induced by retrovirus‐mediated gene transfer of an allogeneic class I gene into syngeneic bone marrow (BM). Using appropriate congenic recombinant mouse strains, we have mapped MHC determinants that are capable of restoring rapid rejection of Kb‐bearing skin grafts. Our results indicate that either a single class I or a single class II alloantigen expressed on skin in association with Kb is able to restore the rapid rejection of Kb ‐mismatched skin grafts. These data suggest that third‐party alloantigens expressed on skin in association with Kb abrogate hyporesponsiveness by providing T cell help. Consistent with this interpretation, spleen cells from mice reconstituted with Kb‐transduced BM were unable to elicit a significant anti‐Kb cytotoxic T lymphocyte response in vitro unless interleukin‐2 was added to the culture medium. Skin graft survival was also analyzed on B10.AKM mice thymectomized 3–4 weeks post‐reconstitution with Kb‐transduced BM. Thymectomy did not result in significantly prolonged survival of B10.MBR skin grafts compared to euthymic controls, suggesting that even early after reconstitution, intrathymic deletion of Kb‐reactive T cells must have been incomplete. Taken together, these data suggest that prolongation of skin allograft survival in this model is controlled at the level of T cell help.
Allergen‐induced recruitment of FcσRI+ eosinophils in human atopic skin
Authors: Barata Luis T. , Ying Sun , Andrew Grant J. , Humbert Marc , Barkans Julia , Meng Qui , Durham Stephen R. , Barry Kay A. 
Published: March 2007

AbstractWe have attempted to identify FcσRI+ eosinophils in cutaneous late‐phase reaction in atopic subjects biopsied at 6, 24 and 48 h after the injection of either allergen or a diluent control. Compared to the diluent sites, allergen‐injected sites had significantly increased numbers of eosinophils, peaking between 6 and 24 h, of which approximately 20–30% expressed mRNA for the α, β, and γ chains of FcσRI, as shown by in situ hybridization. Using either a monoclonal or a polyclonal anti‐α chain antibody, the FcσRIα protein also co‐localized to approximately 50–80% of eosinophils at all time points studied. We also observed a significant correlation (r = 0.89; p = 0.02) between the numbers of FcσRI+ (997+)/EG2+ eosinophils and the magnitude of the late‐phase reaction. Thus, a significant proportion of eosinophils infiltrating the site of allergen‐induced allergic tissue reactions in atopic subjects express FcσRI. The findings show that high‐affinity IgE receptors may play a role in eosinophil secretory processes in vivo.
Lipopeptide immunization without adjuvant induces potent and long‐lasting B, T helper, and cytotoxic T lymphocyte responses against a malaria liver stage antigen in mice and chimpanzees
Authors: Benmohamed Lbachir , Gras‐Masse Héléne , Tartar André , Daubersies Pierre , Brahimi Karima , Bossus Marc , Thomas Alan , Druilhe Pierre 
Published: March 2007

AbstractWe have employed a 26‐amino‐acid synthetic peptide based on Plasmodium falciparum liver stage antigen‐3 to evaluate improvements in immunogenicity mediated by the inclusion of a simple lipid‐conjugated amino acid during peptide synthesis. Comparative immunization by the peptide in Freund's adjuvant or by the lipopeptide in saline shows that the addition of a palmitoyl chain can dramatically increase T helper (Th) cell responses in a wide range of major histocompatibility complex (MHC) class II haplotypes, to the extent that responses were induced in mice otherwise unable to respond to the non‐modified peptide injected with Freund's adjuvant, and that the increased immunogenicity of the lipopeptide led to high and longer lasting antibody production (studied up to 8 months). B and T cell responses induced by the lipopeptide were reactive with native parasite protein epitopes, and a lipopeptide longer than ten amino acids was endogenously processed to associate with MHC class I and elicit cytotoxic T lymphocyte (CTL) responses. Finally, the lipopeptide was safe and highly immunogenic in chimpanzees, whose immune system is very similar to that of humans. Our results suggest that relatively large synthetic peptides, carefully chosen from pertinent areas of proteins and incorporating a simple palmitoyllysine, can induce not only CTL, but also strong Th and antibody responses in genetically diverse populations. Lipopeptides engineered in this way are simple to produce and purify under GMP conditions, they are well tolerated by apes, and with the enhanced immunogenicity without the need for adjuvant that we report here, they offer a quick and relatively low‐cost route to provide material for human malaria vaccination trials.
Magnitude of protein tyrosine phosphorylation‐linked signals determines growth versus death of thymic T lymphocytes
Authors: Akhand Anwarul A. , Pu Meiyi , Du Jun , Kato Masashi , Suzuki Haruhiko , Hamaguchi Michinari , Nakashima Izumi 
Published: March 2007

AbstractUsing concanavalin A (Con A) as a multireceptor‐reactive agonist, we studied the relationship between the growth or death of thymic T lymphocytes and the agonist concentration‐dependent magnitude of the intracellulary delivered signal. Both immature and mature thymic T lymphocytes were subjected to a high concentration of Con A‐mediated signal for apoptotic cell death. In this model, a number of cellular proteins including mitogen activated protein kinases were phosphorylated at tyrosine depending on the concentration of Con A. This effect was followed by corresponding increase in serine 73 phosphorylation of c‐jun and transcription of c‐fos. DNA fragmentation and cell membrane disruption developed concomitantly after stimulation with high concentrations of Con A. The addition of inhibitors of protein kinases which completely inhibited the growth of cells stimulated with low concentrations of Con A only partially prevented death, and even promoted DNA fragmentation of cells stimulated with high concentrations of Con A. The dissociated sensitivities of Con A‐mediated cell growth and cell death to the inhibitors were, however, shown to be due to the different efficiency of inhibition of high and low levels of intracellularly delivered signals. The results indicate that the magnitude of signaling could be the principal element that determines the growth versus death of thymic T lymphocytes.
Partial purification and characterization of a tumor necrosis factor‐α converting activity
Authors: Robache‐Gallea Sylvie , Bruneau Jean‐Michel , Robbe Hugue , Morand Valérie , Capdevila CÉCile , Bhatnagar Neerja , Chouaib Salem , Roman‐Roman Sergio 
Published: March 2007

AbstractTumor necrosis factor (TNF)‐α is initially synthesized as an extracellular membrane‐associated 26‐kDa protein that is further cleaved at Ala76‐Val77 to yield the soluble 17‐kDa form. Recently, peptide‐hydroxamate metallopro‐teinase inhibitors have been reported to block the proteolytic processing of TNF‐α, thus suggesting that the putative TNF‐α converting enzyme (TACE) is a zinc‐dependent metalloendopeptidase. In this report, we characterize a TNF‐α converting activity (TACA) that cleaves in vitro the human 26‐kDa TNF‐α at the physiological processing site. The chromatography steps followed for purification and the use of a panel of proteinase inhibitors indicate that the enzyme responsible for TACA is a membrane glycosylated metalloendopeptidase which is most likely different from the matrix‐degrading metalloproteinases. The failure of TACA to process a Val77→Gly77 precursor mutant emphasizes the importance of hydrophobic residue at P1' position. In addition, TACA is not able to cleave the mouse pro‐TNF‐α and does not catalyze in vitro the processing of other transmembrane proteins susceptible to metalloproteinase‐mediated shedding, such as interleukin‐6 or TNF receptors. These studies suggest the existence of an enzyme specific for TNF‐α within the metalloproteinases involved in the processing/shedding of a number of cytokines and cytokine receptors.
P‐selectin glycoprotein ligand‐1 mediates rolling of mouse bone marrow‐derived mast cells on P‐selectin but not efficiently on E‐selectin
Authors: Steegmaier Martin , Blanks James E. , Borges Eric , Vestweber Dietmar 
Published: March 2007

AbstractIt has been shown recently that mast cells play an essential role as a source of tumor necrosis factor‐α production during neutrophil recruitment to sites of bacterial infection. Increased numbers of mast cells are indeed noted at sites of wound healing and inflammation. These cells are either recruited from the bone marrow or proliferate locally under cytokine stimulation. Little is known about how mast cell progenitors extravasate into tissue. Using antibody‐like fusion proteins of mouse E‐selectin and P‐selectin, we have analyzed the ability of immature mouse bone marrow‐derived mast cells (BMMC) to interact with the endothelial selectins. The P‐selectin glycoprotein ligand‐1 (PSGL‐1) was affinity‐isolated from detergent extracts of surface biotinylated BMMC with both selectin‐IgG fusion proteins. However, only P‐selectin‐IgG, but not E‐selectin‐IgG showed significant interaction with intact BMMC as tested by flow cytometry and cell attachment assays with the immobilized fusion proteins under flow and non‐flow conditions at physiological shear stress. Thus, in spite of carrying the necessary carbohydrate modifications which enable solubilized PSGL‐1 to bind avidly to E‐selectin, PSGL‐1 on the surface of BMMC is presented in a way that prevents it from interacting efficiently with E‐selectin. Affinity‐purified rabbit antibodies against mouse PSGL‐1 almost completely blocked the interaction of BMMC with P‐selectin‐IgG in flow cytometry as well as in cell adhesion assays under static and under flow conditions. Our data reveal that PSGL‐1 is the major binding site for P‐selectin on mouse BMMC progenitors, but does not support efficient interactions with E‐selectin.
The T/B cell interaction involved in induction of the mouse IgG2ah suppression is restricted by major histocompatibility complex class I, but not class II molecules
Authors: Majlessi Laleh , Bordenave Guy 
Published: March 2007

AbstractTo determine the major histocompatibility complex (MHC) restriction of the T/B cell interaction involved in a negative regulation of Ig production, we used mouse model of T cell‐induced IgG2ab suppression in vivo. Normal or specifically triggered T splenocytes from mice of the Igha haplotype, when neonatally transferred into histocompatible Igha/b heterozygotes, are able to induce a specific and total suppression of the IgG2ab allotype. Nevertheless, only transfer of IgG2ab‐primed Igha T splenocytes induces this suppression in Ighb/b homozygous congenic mice in which the whole IgG2a isotype production is inhibited. This suppression is chronically maintained by CD8+ T cells, but can be experimentally reversed. We have established that the suppression induction required a CD4+CD8+ T cell cooperation and operated via the recognition by the involved TCR of Cγ2ab‐derived peptides presented by the target B cells in an MHC haplotype‐restricted manner. Here, by using Ighb mice genetically deficient for MHC class I (β2‐microglobulin%, or β2m%) or class II (I‐Aβ%) molecules, we demonstrate functionally that the suppression induction implicates an MHC class I‐, but not class II‐restricted interaction. Indeed, the anti‐IgG2ab T cells transferred into Ighb H‐2b I‐Aβ% mice carry out the suppression process normally, while in Ighb H‐2b β2m% recipients, their suppression induction capacity is significantly inhibited. Moreover, the Cγ2ab 103–118 peptide, identified as the sole Cγ2ab‐derived peptide able to amplify the anti‐IgG2ab T cell reactivity in Igha H‐2b mice, is also able to stabilize the H‐2Db, but not the H‐2Kb class I molecules at the surface of RMA‐S (TAP2−, H‐2b) cells. These results indicate that, despite the CD4+/CD8+ T cell cooperation during the induction phase of suppression only MHC class I molecule expression is required at the surface of IgG2ab+ B cells for suppression establishment.
Age‐related impaired affinity maturation and differential D‐JH gene usage in human VH6‐expressing B lymphocytes from healthy individuals
Authors: van Dijk‐Härd Iris , Söderström Ingegerd , Feld Sari , Holmberg Dan , Lundkvist Inger 
Published: March 2007

AbstractTo elucidate the basic molecular events underlying humoral immunity during ontogeny and senescence, we analyzed a panel of 179 polymerase chain reaction‐derived VH6‐D‐JH rearrangements from cord blood, peripheral blood, and spleen. Nucleotide sequence analysis of the CDR3 region shows that there is a difference in D and JH gene usage in functional rearrangements between lymphocytes from peripheral blood and spleen. Analysis of the VH6 gene shows that the mutational frequencies rise from 0.81% in cord blood to 1.96% in peripheral blood lymphocytes derived from young adults, and decrease to 0.80% in samples from individuals older than 50 years. The number of rearrangements carrying mutations follows a similar pattern: 22% in cord blood, 73% in the age group 20–49 years, and 57% in the age group over 50 years. The mutational frequencies among the mutated genes are, however, similar for cord blood and young adults, 2.76% and 2.51%, respectively, and 1.3% in older adults. These data show an age‐related impaired affinity maturation which might relate to the decrease in immunological responsiveness among the elderly.
Differential expression of binding sites for chemokine RANTES on human T lymphocytes
Authors: Utsunomiya Iku , Tani Kenji , Gong Wanghua , Oppenheim Joost J. , Wang Ji Ming 
Published: March 2007

AbstractThe C‐C chemokine RANTES, a T lymphocyte chemoattractant, is considered an important mediator of inflammation, allergy, and host defense against HIV‐1 infection. In this study, we investigated the modulation of binding of RANTES to T lymphocytes. Human peripheral blood CD3+ T cells, when freshly isolated from buffy‐coat blood, expressed a considerable number of high‐affinity binding sites for RANTES. These cells also showed significant chemotactic migration in response to RANTES in vitro. After 6–15 h incubation at 37°C, the binding of RANTES, but not of macrophage inflammatory protein‐1α (MIP‐1α) or of monocyte chemotactic protein‐3 (MCP‐3), consistently increased. Scatchard analyses indicated that the number of binding sites for RANTES increased about threefold by 15 h without any change in the affinity. The increase in RANTES binding was no longer detected by 24 h. This increase in the specific binding was mainly attributable to CD4+ T cells and was not associated with increased chemotactic activity of these cells in response to RANTES. Incubation with anti‐CD3 antibody for 15 h markedly reduced the binding capability of T cells for RANTES and was associated with decreased chemotactic activity. On the other hand, when T cells were incubated with interleukin‐2 (IL‐2) for 1 week, the specific binding for all three C‐C chemokines, RANTES, MIP‐1α, and MCP‐3 was markedly increased in comparison to cells cultured in the absence of IL‐2. These results suggest that the expression of binding sites on T cells for RANTES is differentially modulated, indicating the existence of novel receptors for RANTES that do not bind MIP‐1α.
Association between receptor density, cellular activation, and transformation of adhesive behavior of flowing lymphocytes binding to VCAM‐1
Authors: Lalor Patricia F. , Clements John M. , Pigott Rod , Humphries Martin J. , Spragg Julia H. , Nash Gerard B. 
Published: March 2007

AbstractWe investigated the ability of purified vascular cell adhesion molecule‐1 (VCAM‐1), adsorbed on plastic, to capture and immobilize flowing lymphocytes, and the dependence of adhesive behavior on activation of the counter‐receptor, α4β1 integrin. This integrin/immunoglobulin interaction bound lymphocytes at a wall shear stress at which the β2‐integrin family has previously been found ineffective (> 0.1 Pa), and whereas lymphocytes rolled on lower concentrations of VCAM‐1 (10 μg/ml), they were stationary at high concentrations (100 μg/ml). Activation of α4β1 integrin by Mn2+ or by antibody 12G10 or treatment of lymphocytes with phorbol ester caused transformation to stationary adhesion, and increased binding significantly only at the lower concentrations of VCAM‐1. We thus hypothesized that formation of a high density of ligand between VCAM‐1 and α4β1 integrin actively transformed lymphocyte behavior. This concept was supported by the finding that the proportion of lymphocytes rolling on the higher concentrations of VCAM‐1 increased if cells were pretreated with azide to block energy‐dependent responses, or if intracellular Ca2+ was chelated. However, not all activation responses were equivalent: only phorbol ester induced marked spreading of immobilized cells, and if pretreatment was prolonged, this agent even reduced the efficiency of initial attachment of flowing lymphocytes. Azide treatment had no effect on transformation to stationary adhesion caused by Mn2+ or activating antibody. Thus, different forms of lymphocyte activation were identifiable: external modification of integrin converted rolling to stationary attachment, did not require ATP, and was reversible; high‐density ligand binding induced an energy‐dependent signal for conversion from rolling to stationary attachment, but not spreading; and protein kinase C activation promoted stationary attachment and spreading, but not necessarily capture. VCAM‐1 is thus a versatile adhesion receptor capable of supporting all stages of leukocyte attachment, i.e. rolling, stationary, and spreading, and of ligand‐induced transformation of adhesion, although an additional signal appears necessary to promote lymphocyte spreading and migration.