bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deficient antigen processing of a protein quaternary structure can be overcome by receptor‐mediated uptake
Authors: Rouas‐Freiss Nathalie , Housseau Franck , Bidart Jean‐Michel , Bonnerot Christian , Amigorena Sebastien , Guillet Jean‐Gérard , Bellet Dominique 
Published: March 2007

AbstractHuman chorionic gonadotropin (hCG) is a dimer of non‐covalently associated alpha (hCG‐α) and beta (hCG‐β) subunits. This molecule was used to study whether receptor‐mediated uptake influences the presentation of a protein quaternary structure. Unprimed splenocytes and a B cell lymphoma were capable of presenting only the free (hCG‐α) but not the combined (hCG) α subunit to hCG‐α T cell hybridomas, while hCG‐α‐primed lymph node cells (LNC) responded to both hCG‐α and hCG. As antigen (Ag)‐specific antigen‐presenting cells (APC) present in the hCG‐α‐primed LNC population may be potentially effective for presenting hCG, we investigated the role of specific Ag capture, through mIg and FcγR, in the processing and presentation of hCG and hCG‐a to HAG 5, a T cell hybridoma directed against the immunodominant region (amino acids 61‐81) of hCG‐α. Results showed that only B cells bearing membrane immunoglobulin capable of recognizing hCG‐α and hCG, and present in hCG‐α‐primed mice, were extremely effective in presenting the free as well as the combined a subunit. The effect of FcR‐mediated uptake was analyzed using a B cell line transfected with the FcγRII‐B2 gene to present immune complexes of either hCG‐α or hCG. We found that hCG‐α and hCG were presented equally well, whatever the Ag‐binding site of each antibody to hCG or its a subunit. Using HBG 6, an hCG‐β Tcell hybridoma, we performed similar experiments with the FcγRII‐B2 cell line and determined that the potentiation of hCG presentation to HBG 6 was similar to that observed with HAG 5. Then kinetic experiments were performed to examine the effect of Ag uptake through FcR on processing. Results demonstrated that the uptake pathway drastically influenced the expression of α T cell determinants in the αβ dimer. In addition, treatment with cycloheximide, a protein synthesis inhibitor, only impaired the ability of APC to present specifically captured Ag. Thus, the processing pathway for specifically captured Ag might be different from the pathway used to process nonspecifically captured Ag. This observation might explain why receptor‐enhanced uptake bypasses the inefficient processing of the hCG quaternary structure and enables similar efficiency in the presentation of α and β T cell specificities. These findings provide new insight into the antigenicity of oligomeric molecules, which is modified whether antigen capture is specific or not.
Extensive N nucleotide addition in junctional region of T cell receptor Vγ5 genes rearranged in fetal liver‐derived thymocytes in radiation chimera mice
Authors: Matsuzaki Goro , Ogimoto Masaro , Yoshikai Yasunobu , Seki Ritsuko , Nomoto Kikuo 
Published: March 2007

AbstractThe Vγ5 chain of Tcell receptor γδ is preferentially expressed by murine fetal thymocytes. The fetal Vγ5 gene is known to be homogeneous and lacks N nucleotide addition.We previously reported that Vγ5+ cells were detected among donor‐derived thymocytes from irradiated C3H/He mice soon after reconstitution with AKR/J fetal liver (FL) cells, but that only a few Vγ5+ were detected among donor‐derived thymocytes from irradiated C3H/He mice reconstituted with adult bone marrow (ABM) cells. The results suggest that preferential use of Vγ5 is determined at the level of Tcell precursor generation. In the present report, we analyzed whether the junctional region of FL‐derived Vγ5 genes in the FL chimeras is of fetal type. Sequencing analysis showed that Vγ5 genes from FL chimeras contained extensive N nucleotide addition and were diverse both in nucleotide sequences and deduced amino acid sequences. Vγ5 genes from donor‐derived thymocytes of ABM chimeras, which by polymerase chain reaction were revealed to be less frequent than those of FL chimeras, also showed extensive N addition. Furthermore, the terminal deoxynucleotidyl transferase (TdT) gene, which encodes an enzyme that adds N nucleotides into the junctional region, was expressed at high level in the donor‐derived thymocytes of FL chimeras and normal 8‐week‐old AKR/J thymocytes but at low level in day 17 fetal AKR/J thymocytes. Our results suggest that the preferential rearrangement of the Vγ5 gene is determined at the level of Tcell precursor generation but the homogeneous Vγ5 sequence of fetal type is generated only in the fetal thymic microenvironment where TdT gene expression is low or absent.The nomenclature of murine TcR γ chains is according to Reilly et al. (Nature 1986. 321: 878). The relationship between the different nomenclature systems is summarized in Takagaki et al. (J. Immunol. 1989. 141: 2112).
Major histocompatibility complex class I molecules are required for the development of insulitis in non‐obese diabetic mice
Authors: Katz Jonathan , Benoist Christophe , Mathis Diane 
Published: March 2007

AbstractAn early step in the development of autoimmune diabetes is lymphocyte infiltration into the islets of Langerhans of the pancreas, or insulitis. The infiltrate contains both CD4+ and CD8+ T cells and both are required for progression to diabetes in non‐obese diabetic (NOD) mice. It has been thought that the CD4+ lymphocytes are the initiators of the disease, the islet invaders, while CD8+ cells are the effectors, the islet destroyers. We question this interpretation because NOD mice lacking MHC class I molecules, hence CD8+ T cells, do not display even insulitis when expected.
Linomide inhibits programmed cell death of peripheral T cells in vivo
Authors: Gonzal José Angel , Gonźlez‐Garciá Ana , Kalland Terje , Hedlund Gunnar , Martínez‐A Carlos , Kroemer Guido 
Published: March 2007

AbstractProgrammed cell death (PCD) is involved in the physiological regulation of lymphocyte turnover, as well in the antigen‐driven selection of T and B cells. Here it is shown that the immunomodulator linomide (quinoline‐3‐carboxamide) inhibits the apoptotic decay of peripheral T lymphocytes in response to three different stimuli. First, linomide reduces the superantigen‐mediated apoptosis and deletion of specific T lymphocytes of both the CD4+ and the CD8+ subsets without affecting other superantigen‐triggered phenomena such as T cell expansion and anergy. Second, linomide abolishes the T lymphopenia and inhibits PCD of splenic CD4+ and CD8+ T cells induced by exogenous glucocorticoids. This effect is restricted to peripheral T lymphocytes and does not concern thymocytes. Finally, linomide abolishes the development of lymphopenia that follows infection with vaccinia virus, while reducing PCD of CD4+ and CD8+ peripheral T cells. The anti‐apoptotic effect of linomide could account for its immunostimulatory properties and might be relevant to the treatment of immunodeficiencies associated with an increased apoptotic decay of T lymphocytes.
Humoral immune response to 2,4‐dinitrophenyl ‐‐ keyhole limpet hemocyanin in antigen‐free, germ‐free and conventional BALB/c mice
Authors: Bos Nicolaas A. , Ploplis Victoria A. 
Published: March 2007

AbstractThe B cell immune response to 2,4‐dinitrophenyl (DNP) keyhole limpet hemocyanin was compared in antigen‐free, germ‐free and conventional BALB/c mice. The numbers of total and of DNP‐specific IgM‐, IgG‐ and IgA‐secreting cells in the spleen were determined by enzyme‐linked immunosorbent plaque assays after primary, secondary and hyperimmunization. Three days after primary immunization a peak of DNP‐specific IgM‐secreting cells was seen in conventional mice only. However, this specific response was accompanied by a rise in the total number of IgM‐secreting cells. At day 6 after primary immunization the total number and the frequency of DNP‐specific IgG‐secreting cells were higher in antigen‐free mice, compared to germ‐free and conventional mice. After secondary immunization in conventional mice only, a considerable bystander IgG response was seen together with the DNP‐specific IgG response. At the end of the secondary response 90% of all IgG‐secreting cells were DNP specific in antigen‐free mice, while the corresponding figure in germ‐free and conventional mice was 63% and 14%, respectively. After hyperimmunization, the absolute number of DNP‐specific IgG‐secreting cells in the spleen was 5‐fold and 11‐fold higher in antigen‐free mice then in germ‐free and conventional mice, respectively. Approximately 48% of all IgG‐secreting cells were DNP specific in antigen‐free mice, while the corresponding figure in germ‐free and conventional mice was 17% and 12%, respectively. The results show that the exogenous antigenic load of animals influences the immune response to newly introduced antigens. The higher absolute and relative numbers of antigen‐specific IgG‐secreting cells after hyperimmunization in antigen‐free mice compared to germ‐free and conventional mice may provide a better source for antigen‐specific B cells that eventually can be used for hybridoma production.
On the biological origin of anti‐double‐stranded (ds)DNA antibodies: systemic lupus erythematosus‐related anti‐dsDNA antibodies are induced by polyomavirus BK in lupus‐prone (NZBxNZW) F1 hybrids, but not in normal mice
Authors: Fredriksen Knut , Osei Awuku , Sundsfjord Arnfinn , Traavik Terje , Rekvig Ole Petter 
Published: March 2007

AbstractWe have recently demonstrated that polyomavirus BK and isolated BK double‐stranded (ds)DNA have a strong potential for induction of anti‐dsDNA antibodies. Here, data are presented that demonstrate that normal mice (a term used in this report for mice not predisposed to a lupus‐like syndrome) of four different strains responded to both BK virus and BK dsDNA by producing transient antibodies binding preferentially to the viral dsDNA itself. These antibodies did not bind in the Crithidia luciliae assay, and did not seem to be of pathogenic significance, as neither signs of proteinuria nor immunochemical signs of glomerulonephritis developed in these mice. In contrast, 5‐week‐old (NZBxNZW)F1 mice developed strong and persistent anti‐dsDNA antibodies in response to BK virus and BK dsDNA, with similar features to those of anti‐dsDNA antibodies from individuals with systemic lupus erythematosus: they reacted strongly in the Crithidia luciliae assay and cross‐reacted with viral as well as with mammalian dsDNA. Furthermore, persistent proteinuria and glomerulonephritis, with demonstrable heavy mesangial deposits of immune complexes containing IgG anti‐dsDNA antibodies, developed 2‐‐3 months earlier than in spontaneously autoimmune control mice. The relevance of these observations to a viral origin of anti‐dsDNA antibodies in lupus is discussed.
Tyrosine phosphorylation of α tubulin in human T lymphocytes
Authors: Ley Steven C. , Verbi Winston , Pappin Darryl J. C. , Druker Brian , Davies Adelina A. , Crumpton Michael J. 
Published: March 2007

AbstractN‐terminal sequencing of the 55‐ and 50‐kDa polypeptides affinity purified on a phosphotyrosine monoclonal antibody column from activated Jurkat T cells identified α and β tubulin. Two‐dimensional gel analysis indicated that α tubulin was directly phosphorylated on tyrosine. β Tubulin was not detectably tyrosine phosphorylated but was precipitated by anti‐phosphotyrosine (PTyr) antibody by virtue of its association with the α subunit as a heterodimer. Phosphotyrosyl α tubulin was not incorporated into intact microtubules and was all in the unpolymerized soluble fraction. These results suggest that tyrosine phosphorylation of α tubulin may inhibit the ability of this subunit to polymerize into microtubules. Stimulation of Jurkat T cells via T cell receptor increased the amount of tubulin precipitated by the anti‐PTyr antibody. These data raise the possibility that the polymerization of tubulin heterodimers may be regulated by phosphorylation on tyrosine during T cell activation.
Th1 and Th2 CD4+ T cell clones specific for Plasmodium chabaudi but not for an unrelated antigen protect against blood stage P. chabaudi infection
Authors: Taylor‐Robinson Andrew W. , Phillips R. Stephen 
Published: March 2007

AbstractThe host protective immune response to blood stage malaria infection was studied using Plasmodium chabaudi chabaudi (P. chabaudi) in NIH mice. It has been shown previously that CD4+ cells are critically required for protection against erythrocytic infection. Mice lacking a functional CD4+ cell compartment suffer unremitting patent primary parasitemias for at least 60 days after infection. Here, we report that the adoptive transfer of eight P. chabaudi‐specific CD4+ T cell clones of either the Th1 or Th2 type to mice rendered CD4‐depleted by adult thymectomy and anti‐CD4 monoclonal antibody therapy fully restored the ability of recipients to control challenge infection. Control Th1 and Th2 clones specific for an unrelated antigen, ovalbumin, were unable to confer a comparable level of protection in CD4‐depleted mice, even though they received regular doses of the antigen. These data demonstrate that protective immunity to asexual P. chabaudi parasites can be mediated through immune CD4+ T cell clones of either the Th1 or the Th2 subset.
Activation of peripheral large granular lymphocytes with the serine/threonine phosphatase inhibitor, okadaic acid
Authors: McVicar Daniel W. , Mason Anna T. , Bere Earl W. , Ortaldo John R. 
Published: March 2007

AbstractThe murine polyether fatty acid, okadaic acid, is a potent inhibitor of serine/threonine phosphatases in eukaryotic cells. This compound inhibits both protein phosphatase 1 (PP1) and phosphatase 2A (PP2A). Here we have examined the potential of okadaic acid as an activator of fresh peripheral CD3‐ large granular lymphocytes (LGL). We demonstrate that overnight exposure of LGL to as little as 1 nM okadaic acid induced an increase in natural killing against the K562 cell line, but does not induce LAK activity. Optimal cytotoxic activation (2‐fold) occurred at 0.01‐‐1.0 nM okadaic acid, with a return to baseline levels at 10‐‐20 nM, and inhibition, likely due to toxicity, at 40 nM. In addition, okadaic acid at doses ⩾20 nM induced LGL but not T cells to produce interferon‐γ. Similar to phorbol esters, overnight incubation with okadaic acid causes a dose‐dependent reduction in expression of the low‐affinity receptor for the Fc portion of IgG (CD16). However, unlike phorbol ester, short‐term (5 min) okadaic acid treatment did not block CD16‐mediated Ca2+ mobilization in LGL. To address the underlying biochemical mechanisms of okadaic acid activities, the levels of several as‐yet‐unidentified serine/threonine kinases were assayed after renaturation. Under these conditions, okadaic acid induced similar increases in kinase levels in both T cells and LGL. Taken together, these data suggest an important role for PP1 and PP2A in LGL physiology, and define okadaic acid as a potentially important biological response modifier for the study of LGL and Tcell biochemistry, signal transduction, and transcriptional regulation.
Generation of chimeric C5a/formyl peptide receptors: towards the identification of the human C5a receptor binding site
Authors: Pease James E. , Burton Dennis R. , Barker Michael D. 
Published: March 2007

AbstractWe employed the polymerase chain reaction to produce a series of chimeric C5a/formyl peptide receptors. Chinese hamster ovary cells transfected with these constructs were tested for their ability to bind C5a. Substitution of three of the extracellular domains of the C5a receptor with the corresponding domains of the formyl peptide receptor abolished C5a binding, whilst replacement of the first extracellular loop of the C5a receptor with that of the formyl peptide receptor had little effect on the affinity of the receptor for C5a. We therefore conclude that this first outer loop of the C5a receptor does not participate in ligand binding, whilst involvement of the other extracellular domains of the receptor cannot be ruled out.
Ultrastructural analysis of thymic nurse cell epithelium
Authors: Penninger Josef , Rieker Theresa , Romani Nikolaus , Klima Joerg , Salvenmoser Willi , Dietrich Hermann , Stössel Hella , Wick Georg 
Published: March 2007

AbstractThymic nurse cells (TNC), a paradigmatic cell type of cortical epithelium, are large lymphoid‐epithelial cell complexes of thymocytes enclosed within vacuoles lined by the epithelial cell membrane. TNC express major histocompatibility complex (MHC) class I and class II molecules on their surface and vacuole‐lining membranes at high density and it was suggested that TNC provide an optimal microenvironment for positive selection of T cells. In this report we present electron microscopical data demonstrating that chicken TNC display morphological structures of exocytosis previously shown for hormone‐secreting cells. In TNC, however, exocytosis is restricted to the capillary cleft between the epithelial cell and engulfed thymocytes. Thus, besides physical contact between the epithelial cell and enclosed thymocytes, TNC may additionally influence the development of thymocytes through release of soluble factors in a restricted microenvironment. By employing the 3‐(2,4‐dinitroanilino)‐3‐amino‐N‐methyl‐propylamine technique which at the ultrastructural level detects acidic organelles involved in processing of antigens presented by MHC class II molecules, we also show that TNC contain acidic compartments similar to classical antigen‐presenting cells, i.e. early and late endosomes and lysosomes, albeit in a lower amount than in thymic dendritic cells. This fact provides evidence that TNC not only are capable of antigen presentation but also possess the intracellular machinery for antigen processing.
Involvement of gp130/interleukin‐6 receptor transducing component in interleukin‐11 receptor
Authors: Fourcin Maryvonne , Chevalier Sylvie , Lebrun Jean‐Jacques , Kelly Paul , Pouplard Annick , Wijdenes John , Gascan Hugues 
Published: March 2007

AbstractThe recently cloned interleukin (IL)‐11 displays many biological properties in common with those reported for IL‐6. In order to analyze the nature and the functionality of the IL‐11 receptor we developed a proliferative assay using the human multifactor‐dependent cell line TF1. We showed that a blocking monoclonal antibody GPX7 raised against the gp130/IL‐6 receptor transducing subunit was also able to inhibit the IL‐11‐triggered TF1 line proliferation. In addition, involvement of gp130 in IL‐11 signaling was demonstrated by an induction of the transducing protein phosphorylation in response to IL‐11, as observed for IL‐6. In contrast, the blocking monoclonal antibody B‐R6, which recognized the gp80/IL‐6 binding subunit, failed to interfere with the IL‐11 proliferative signal in the TF1 cell line. Similarly, we did not observe any competition between IL‐6 and IL‐11 for a putative common binding site on the cell surface. These results suggest that the IL‐11 binding component is different from the gp80/IL‐6 receptor. In conclusion, IL‐11, along with IL‐6, leukemia inhibitory factor, oncostatin M and ciliary neurotrophic factor, belongs to the same family of cytokines, using gp130 as a transducing protein.
Prenylated proteins and lymphocyte proliferation: Inhibition by d‐limonene and related monoterpenes
Authors: Schulz Stefan , Bühling Frank , Ansorge Siegfried 
Published: March 2007

AbstractThe aim of the present study was to explore the role of post‐translational isoprenoid modification of cellular proteins in the proliferation of human lymphocytes. We here report that treatment of phytohemagglutinin‐stimulated peripheral blood mononuclear cells with monoterpenes including d‐limonene, perillic acid and perillyl alcohol (0.5–5 mM) which selectively inhibit the isoprenylation of 21–26‐kDa proteins resulted in a dose‐dependent inhibition of DNA synthesis. Cell cycle analysis revealed that perillic acid arrested cells in G1 and prevented cells from entering S phase in a manner similar to that induced by the specific 3‐hydroxy‐3‐methylglutaryl‐CoA reductase inhibitor, compactin. However, unlike compactin, the perillic acid‐induced effects on lymphocyte proliferation were not prevented by addition of mevalonate. We also examined the incorporation of [3H]mevalonate into proteins in resting and phytohemagglutinin‐stimulated lymphocytes during the first 30 h of culture. While in unstimulated lymphocytes radioactivity was predominantly incorporated into a cluster of 21–26‐kDa proteins, mitogenic stimulation was associated with a striking increase in [3H]mevalonate incorporation into a protein (≈︁68 kDa) with migration characteristics similar to that of nuclear lamin B. Treatment of phytohemagglutinin‐stimulated lymphocytes with 5 mM d‐limonene, 2.5 mM perillic acid or 1.25 mM perillyl alcohol strongly suppressed [3H]mevalonate‐labeling of proteins to a degree that correlated with the level of DNA synthesis inhibition. These findings suggest that those mevalonate‐derived products required for lymphocyte proliferation may include one or more isoprenylated proteins and that the isoprenylation of these proteins is required for cell cycle progression.
T cell long‐term hyporesponsiveness follows antigen receptor engagement and results from defective signal transduction
Authors: Dubois Patrice M. , Andris Fabienne , Urbain Jacques , Leo Oberdan , Kaufman Marcelle , Shapiro Robert A. , Gilliland Lisa K. , Ledbetter Jeffrey A. 
Published: March 2007

AbstractT cell receptor (TCR)‐mediated stimulation of T hybridomas leads to cell activation and lymphokine production that is followed by a long‐term hyporesponsiveness. To investigate the biochemical events involved in the induction and maintenance of this antigen receptor hyporesponsiveness or anergy, we have expressed a G protein/PLCβ1‐coupled muscarinic subtype 1 acetylcholine receptor in a murine T cell hybrid. Transfected cells were capable of responding to both muscarinic agonists and TCR ligands by inducing interleukin‐2 secretion that was sensitive to cyclosporin A and dexamethasone. Both receptors induced tyrosine kinase (TK) activity, but muscarinic stimulation did not affect tyrosine phosphorylation of PLCγ1, nor did the TK inhibitor, herbimycin, block muscarinic receptor‐mediated calcium mobilization. These data indicate that in T cells, the muscarinic receptor mediates T cell effector functions by regulating a TK‐independent proximal pathway which later converges with the TCR pathway. Using these cells, we have explored the long‐term consequences of T cell stimulation via antigen or muscarinic receptors. Our results show that hyporesponsiveness specifically follows TCR engagement and appears to result from a defect in the early signal transduction initiated by TCR cross‐linking. A study of TCR‐mediated signaling supports this model by showing that tyrosine phosphorylation and calcium mobilization are deficient in hyporesponsive T cells.