bluuebunny/crossref_metadata_2025_split huggingface dataset:
Restricted T cell receptor usage in DA rats during early collagen‐induced arthritis
Authors: Erlandsson Helena , Müsseneru Åsa , Klareskogu Lars , Goldf Daniel P. 
Published: March 2007

AbstractWe have investigated the usage of T cell receptor (TcR) Vβ gene structures in DA rats undergoing homologous collagen‐induced arthritis induced by immunization with homologous collagen type II emulsified in Freund's incomplete adjuvant. TcR Vβ expression within freshly isolated inflamed synovial tissue (ST) and primary draining lymph nodes was analyzed in a semi‐quantitative polymerase chain reaction assay. A highly restricted TcR Vβ gene expression was observed in ST samples 2 days after onset of clinical disease, with Vβ6, 8.2 and 8.5 comprising more than 60% of the total Vβ expression measured. The corresponding primary draining lymph nodes from the diseased animals showed some bias in Vβ expression at this time but not as remarkable as that found in ST. One week after onset of disease, consistent Vβ gene bias was much less evident in either site. These results indicate that T cells which infiltrate synovia early in disease are highly restricted with respect to Vβ expression.
A human CD4 transgene rescues CD4−CD8+ cells in β2‐microglobulin‐deficient mice
Authors: Baron Agnès , Hafen Katrin , von Boehmer Harald 
Published: March 2007

AbstractThe specificity of the αβ T cell receptor for class I or class II major histocompatibility complex (MHC) molecules determines whether a mature T cell will be of the CD4−CD8+ or CD4+CD8− phenotype, respectively. We show here that a human CD4 transgene can rescue a significant fraction of CD4−CD8+ T cells in β2‐microglobulin‐deficient mice. Cells with this phenotype could be induced to become potent killers of targets expressing allogeneic MHC antigens, indicating that lineage commitment can precede the rescue of developing cells by the T cell receptor for antigen and the CD4 coreceptor.
Defective lymphokine production by most CD8+ and CD4+ tumor‐specific T cell clones derived from human melanoma‐infiltrating lymphocytes in response to autologous tumor cells in vitro
Authors: Guilloux Yannick , Viret Christophe , Gervois Nadine , Dréan Eric Le , Pandolfino Marie‐Christine , Diez Elisabeth , Jotereau Francine 
Published: March 2007

AbstractHuman melanomas are infiltrated by tumor‐reactive T lymphocytes. However, the ability of these cells to elicit a specific anti‐tumor response in vivo remains to be established. Because lymphokine production is critical for T cell functions, we have analyzed the capacity of melanoma‐specific tumor‐infiltrating lymphocyte (TIL) clones to produce major lymphokines: interleukin‐2 (IL‐2), interferon‐γ (IFN‐γ) and interleukin‐4 (IL‐4), as well as tumor necrosis factor (TNF), in response to direct antigen presentation by autologous and allogeneic tumor cells. We report here that, upon stimulation by autologous melanoma cells, all TIL clones secreted TNF but only a few of them produced significant amounts of IL‐2, IL‐4 or IFN‐γ. Nonetheless, all these clones consistently produced two or three of these last lymphokines upon stimulation with phorbol myristate acetate and calcium ionophore, as well as IL‐2 upon CD3 stimulation, showing the existence of three lymphokine profiles among them: Th1, Th0 and a profile characterized by IL‐2 and IL‐4, but not IFN‐γ secretion. Stimulation of TIL clones by allogeneic melanoma lines sharing the appropriate HLA‐peptide complexes revealed that defective IL‐2 production seemed to be a constant feature for some clones, while it was, for other clones, dependent on the antigen‐presenting tumor cells. For this last type of clone, we further showed that defective IL‐2 induction resulted from an LFA‐3 defect of some melanoma cells or from distinct yet undefined defects of other melanoma lines. Our data suggest that defective lymphokine secretion may be an essential component of the in vivo failure of melanoma‐reactive TIL to control tumor development. Interestingly both CD4+ and CD8+ TIL clones from one patient were fully activated by the autologous melanoma cells in vitro, supporting a potential role of such TIL in spontaneous or induced tumor rejection.
Evidence for a selective and multi‐step model of T cell differentiation: CD4+CD8low thymocytes selected by a transgenic T cell receptor on major histocompatibility complex class I molecules
Authors: Pircher Hanspeter , Ohashi Pamela S. , Boyd Richard L. , Hengartner Hans , Brduscha Karin 
Published: March 2007

AbstractWe have characterized a prominent (15‐20 %) thymocyte population expressing CD4 at a high and CD8 at a low level “CD4+8lo” in mice transgenic for a T cell receptor “TCR” restricted by major histocompatibility complex “MHC” class I molecules. The results demonstrate that the CD4+8lo population is an intermediate stage between immature CD4+8+ and end‐stage CD4+8‐ thymocytes and that the survival of these cells crucially depends on the successful interaction of the transgenic TCR with self MHC class I molecules. In addition we demonstrate that the avidity of the interaction between TCR and self MHC class I molecules determines whether CD4+8lo thymocytes are found in significant numbers in this transgenic model. Our findings support a selective and multi‐step model of T cell differentiation in the thymus.
Signaling properties of anti‐immunoglobulin — resistant variants of WEHI‐231 B lymphoma cells
Authors: Benhamou Laure E. , Watanabe Takeshi , Kitamura Daisuke , Cazenave Pierre‐André , Sarthou Pierre 
Published: March 2007

AbstractStimulation of the B cell antigen receptor (BCR) of the murine immature WEHI‐231 B lymphoma with anti‐immunoglobulin antibodies leads to irreversible growth arrest and apoptosis. As in normal B cells, membrane immunoglobulin (mIg) ligation in WEHI‐231 cells triggers a series of signaling cascades from the BCR to intracellular compartments. In order to address the role of early signals in mediating the growth arrest of WEHI‐231 cells, we have generated two variants resistant to the anti‐Ig‐mediated inhibitory effect. Some of the properties of these variants have been recently described in terms of bcl‐2 and c‐myc gene regulation. We report here that these variants can be further distinguished from the wild type on the basis of significant alterations in the early biochemical events which follow mIg ligation. Both Ca2+ signals and patterns of protein tyrosine phosphorylation were affected in these variants, suggesting that alterations in the early signal transduction machinery may have profound effects on the fate of B cells. In addition, we found that expression of the p75HSI substrate of p53/56lyn was strikingly reduced in both variants as compared to the wild type. These findings support the view that p75HSI may play a critical role in BCR‐dependent signaling cascades.
Promiscuous T cell recognition of an H‐2 IA‐presented mycobacterial epitope
Authors: Vordermeier H. Martin , Harris David P. , Moreno Carlos , Ivanyi Juraj 
Published: March 2007

AbstractGenetically permissive T cell epitopes are an important prerequisite for the development of peptide‐based vaccines or immunodiagnostic reagents. We have investigated the structural requirements of permissive T cell recognition of peptide p350—369 from the 38‐kDa antigen of Mycobacterium tuberculosis. This peptide was found to be immunogenic in mice of the H‐2b, bm12, d. s and k, but not of the H‐2f genotype. T cell responses were restricted by I‐A class II molecules. The same epitope core was recognized in the H‐2b, d and k genotypes. T cell hybrids from BALB/c and C57BL/10 mice were used to determine: (i) the critical residues using substituted peptide derivatives and (ii) the degree of T cell promiscuity. Two out of five BALB (H‐2d)‐derived hybridomas tested displayed promiscuous peptide recognition in the context of H‐2b and H‐2bm12 antigen‐presenting cells. The recognition of critical residues was found to be uniform for all five hybridomas when tested with syngeneic antigen‐presenting cells; additional critical residues were identified when the peptide was recognized in the context of allogeneic antigen‐presenting cells. Only one of the four tested C57BL/10 (H‐2b) hybridomas showed promiscuity in the context of H‐2bm12. Each of these C57BL/10‐derived clones had a distinct response profile toward the critical residues. We propose that the demonstrated T cell promiscuity involves peptide interaction with polymorphic H‐2 I‐A residues.
Injection of detergent‐denatured ovalbumin primes murine class I‐restricted cytotoxic T cells in vivo
Authors: Schibeck Reinhold , Böhm Waltraud , Reimann Jörg 
Published: March 2007

AbstractComplex adjuvant formulations have been used to introduce soluble protein antigens into the “endogenous” processing pathway and hence to elicit specific, major histocompatibility complex class I‐restricted cytotoxic T lymphocyte (CTL) responses. We tested if simple modifications of a model protein antigen, i.e. ovalbumin (OVA), can render it immunogenic for murine class I‐restricted CTL when injected into mice in soluble form. Injection of 1—100 μg native OVA into C57BL/6 (H‐2b) mice did not stimulate a class I‐restricted CTL response. In contrast, immunization of mice with 0.5 to 10 μg sodium dodecyl sulfate (SDS)‐or deoxycholate (DOC)‐denatured OVA efficiently primed CD8+ CTL specific for the well‐characterized Kb‐restricted OVA257—264 epitope. Gel‐purified SDS‐denatured OVA devoid of protein fragments and excess detergent efficiently stimulated a specific CTL response in vivo. OVA preparations denatured by heat or urea treatment were not immunogenic for murine CTL. Injection of non‐treated or detergent‐treated, antigenic OVA257—264 peptide into mice did not elicit a CTL response. Thus, denaturation of OVA by simple detergents such as SDS or DOC dramatically enhances its immunogenicity for class I‐restricted CTL but not all modes of denaturation are equally effective.
Human granzyme B is essential for DNA fragmentation of susceptible target cells
Authors: Su Bin , Bochan Markian R. , Hanna William L. , Froelich Christopher J. , Brahmi Zacharie 
Published: March 2007

AbstractWe have partially characterized the granules of the human NK cell line, YT‐INDY, and assessed granule‐mediated lysis and DNA fragmentation of assorted targets. Biochemical studies demonstrated significant quantities of granzyme B (asp‐ase) and a heretofore undescribed chymase but no tryptase (i.e., granzyme A or 3) or distinct met‐ase. YT‐INDY expressed mRNA for granzyme B, perforin and CCPX. The existence of perforin was confirmed by immunoblot. The granules lysed both human and murine NK‐sensitive and NK‐resistant targets. YTindependent lytic pathway is associated with the granules. In addition, 4‐(2‐aminoethyl) benzenesulfonylfluoride hydrochloride (AEBSF), an inhibitor that selectively blocked the chymase and 3,4‐dichloroisocoumarin (DCI), an inhibitor that inactivated both chymase and asp‐ase activities, marginally affected lysis. By gel electrophoresis and 125I‐labeled deoxyuridine release assay, only murine cells (SP2/0 and YAC‐1) underwent DNA fragmentation, and cleavage was completely inhibited by DCI, whereas EGTA, AEBSF and aurintricarboxylic acid (ATA) had no effect. The results, therefore, underscore the central role of granzyme B in granule‐mediated DNA fragmentation, emphasize that the protease acts via an ATA‐resistant endonuclease pathway and stress that nucleolysis does not invariably accompany granule‐mediated cytolysis. Finally, ATA inhibited the asp‐ase activity of isolated but not granule‐associated granzyme B. ATA, therefore, is not a specific endonuclease inhibitor and results obtained with ATA should be viewed cautiously.
Different cytokine production profiles of γδ T cell clones: Relation to inflammatory arthritis
Authors: Chomarat Pascale , Kjeldsen‐Kragh Jens , Quayle Alison J. , Natvig Jacob B. , Miossec Pierre 
Published: March 2007

AbstractThis study was performed to investigate whether γδ T cells could also be divided into subsets, identified by a cytokine profile, as described for αβ T helper (Th) cell subsets. Cytokine production was studied in 22 γδ T cell clones obtained from the synovial fluid and peripheral blood of one patient with inflammatory arthritis and compared to that of 26 αβ T cell clones of the same and different patients. Interferon‐γ (IFN‐γ) was produced by 18 (82%) and interleukin‐4 (IL‐4) by 17 (77%) out of 22 γδ T cell clones, respectively. In contrast, IL‐10 was not produced, except at very low level in one case. The mean levels of IL‐4 were lower for clones derived from synovial fluid. When considering the production of IFN‐γ as an indicator of Th1 and that of IL‐4 as an indicator of Th2, respectively, the most common pattern was a γδTh1‐like pattern, with the combination of high levels of IFN‐γ and low levels of IL‐4. This pattern was found in Vδ1+ clones, all from synovial fluid. Additional patterns were also observed: a mixed, probably γδ Th0‐like pattern with a more balanced production of both IFN‐γ and IL‐4; a γδTh1 pattern with the production of IFN‐γ alone; a γδTh2 pattern with the production of IL‐4 alone. These three patterns were also seen in blood γδ T cells which were all Vδ2, indicating that these patterns were independent of the γδ phenotype. γδ T cell clones produced lower levels of IFN‐γ (p = 0.001) and higher levels of IL‐4 than αβ clones (p < 0.02). These differences in cytokine production between αβ and γδ subsets and within these subsets may contribute to their respective role in chronic inflammation.
Antigen‐driven tissue‐specific suppression following oral tolerance: Orally administered myelin basic protein suppresses proteolipid protein‐induced experimental autoimmune encephalomyelitis in the SJL mouse
Authors: Al‐Sabbagh Ahmad , Miller Ariel , Santos Leonilda M. B. , Weiner Howard L. 
Published: March 2007

AbstractImmunomodulatory treatment paradigms have been applied to animal models of T cell‐mediated autoimmune diseases in an attempt to develop an immunospecific and non‐toxic form of therapy which can be applied to humans. These treatment paradigms are often directed to T cells with a restricted T cell receptor repertoire or that react with dominant peptide determinants. Experimental data, however, suggests that even if the initial T cell response is restricted to a specific self‐protein in the target organ, spreading autoimmunity may develop with broadening of T cell autoreactivity to additional epitopes of the same autoantigen or to different autoantigens in the target organ. Thus, multiple autoantigens may become targets of the autoimmune response. This makes immunotherapeutic strategies based on suppressing responses to restricted proteins or clones of cells problematic. We have previously shown that suppression of experimental autoimmune encephalomyelitis (EAE) in the Lewis rat by oral myelin basic protein (MBP) is mediated by the release of transforming growth factor‐β after triggering by the oral tolerogen. Here, we report that in the SJL model of EAE oral administration of an autoantigen from the target tissue suppresses disease independent of whether it is or is not the inciting antigen. Thus, orally administered MBP or MBP peptides suppress proteolipid protein (PLP)‐induced EAE, whereas intravenously administered MBP does not. Both oral and intravenous PLP, however, suppressed PLP disease. These findings have important implications for the use of oral tolerance as a therapeutic approach for the treatment of T cell‐mediated inflammatory autoimmune diseases in man in which the inciting autoantigen is unknown or in which there is autoreactivity to multiple autoantigens in the target tissue.
Major histocompatibility complex class I allele‐specific peptide libraries: Identification of peptides that mimic an H‐Y T cell epitope
Authors: Gavin Marc A. , Dere Beverley , Grandea Andres G. , Hogquist Kristin A. , Bevan Michael J. 
Published: March 2007

AbstractWe describe a novel method for screening large libraries of random peptides for T cell antigens. Two libraries were constructed, containing fixed amino acids representing the major histocompatibility complex (MHC) class I anchor residues for H‐2Kb‐restricted octamers and H‐2Db‐restricted nonamers. Peptides from the Kb‐restricted library (KbL: SXIXFXXL) and the Db‐restricted library (DbL: XXXXNXXXIM) specifically stabilize empty Kb and Db molecules, respectively. The libraries contain peptides that mimic several H‐2b‐restricted cytotoxic T lymphocyte epitopes, and 21 mimotopes for a Db‐restricted H‐Y epitope were isolated. A degenerate synthetic peptide of limited complexity containing the identified H‐Y sequence motif was found to be similar to the natural H‐Y epitope by reverse‐phase high performance liquid chromatography analysis. This peptide is also capable of immunizing female mice against male splenocytes. Several applications for MHC‐restricted peptide libraries are discussed.
Selective inhibition of E‐selectin, ICAM‐1, and VCAM in endothelial cells
Authors: Stuhlmeier Karl M. , Csizmadia Vilmos , Cheng Qi , Winkler Hans , Bach Fritz H. 
Published: March 2007

AbstractEndothelial cells, as they normally exist in the vasculature as quiescent cells, perform several functions. In an inflammatory response, endothelial cells are activated to up‐regulate a number of genes, including E‐selectin (ELAM‐1), VCAM‐1, ICAM‐1, interleukin (IL)‐1, IL‐8 and plasminogen activator inhibitor‐1 (PAI‐1). Very little is known about factors that regulate the activation process. We describe here that a heat‐stable protein, normally present in the α‐globulin fraction of serum, inhibits induced expression of E‐selectin, ICAM‐1, and VCAM‐1 in vitro and also impedes the accumulation of mRNA for these molecules. Inhibition of E‐selectin, the only gene tested in this respect, is at the level of transcription. At the same time, the α‐globulins do not, under the same conditions, repress mRNA accumulation for IL‐1, IL‐8, or PAI‐1. The effect of the inhibitor does not relate to constraints on function of nuclear‐factor χB, the induced activity of which is not interfered with at the early time points at which the suppression of these three genes is seen.
Exploring myelin basic protein for HLA class I‐binding sequences
Authors: Tanigaki Nobuyuki , Fruci Doriana , Groome Niegel , Butler Richard H. , Londei Marco , Tosi Roberto 
Published: March 2007

AbstractIn view of the increasing evidence of the involvement of CD8+ T cells in the pathogenesis of multiple sclerosis (MS), we have scanned the sequence of the myelin basic protein (MBP), using 162 overlapping nonapeptides, for HLA‐class I binding sites. Peptide binding was measured using the recently reported HLA class I α‐chain‐refolding assay, and the following HLA allelic products were analyzed: HLA‐A2 (*0201, *0204), B27 (*2705), B35, B51, and B62. A considerable number of binding peptides were distinguished for each of the allelic products tested. In addition, three interesting points emerged. The first was the identification of several binding peptides which did not contain the known anchor motifs. The second was the evidence that several peptides showed a promiscuous binding profile, being able to bind to different HLA class I molecules that were either allelic or non allelic. The third was that in several cases two consecutive peptides could bind to the same HLA molecule.
Homotypic aggregation of CD103 (αEβ7)+ lymphocytes by an anti‐CD103 antibody, HML‐4
Authors: Benmerah Alexandre , Badrichani Anne , Ngohou Kalyane , Mégarbané Bruno , Bègue Bernadette , Cerf‐Bensussan Nadine 
Published: March 2007

AbstractOne monoclonal antibody, HML‐4, directed against the αEβ7 integrin (CD103), an integrin preferentially expressed on human intestinal intraepithelial lymphocytes (IEL), induced the homotypic aggregation of IEL and of a CD103+ MOLT16 cell line. Aggregation was an active adhesion event dependent on an intact cytoskeleton, on tyrosine phosphorylation but not on activation of protein kinase C. It was blocked by four other anti‐CD103 antibodies but by none of the antibodies blocking known adhesion lymphocyte pathways. It was associated with a redistribution of the CD103 integrin in the areas of cell‐cell contacts. These results indicated that HML‐4zx‐induced homotypic adhesion was mediated via CD103 and resulted from the binding of the integrin to an as yet undefined ligand expressed by CD103+ cells. This ligand was distinct from the epithelial ligand of CD103: in contrast with homotypic adhesion, heterotypic adhesion of CD103+ MOLT16 cells on two epithelial intestinal cell lines (DLD1 and HT29) was dependent on the presence of divalent cations, was not enhanced by HML‐4, was inhibited by HML‐1 but not by the three other antibodies with an inhibitory effect on homotypic adhesion. Finally, the study of conjugates between CD103+ and CD103‐ sublines derived from the MOLT16 cell line suggested that HML‐4‐induced homotypic aggregation resulted from homophilic CD103‐CD103 interactions.
Vasoactive intestinal peptide specifically induces human IgA1 and IgA2 production
Authors: Kimata Hajime , Fujimoto Masayuki 
Published: March 2007

AbstractThe effects of vasoactive intestinal peptide (VIP) on human IgA1 and IgA2 production were studied. In unfractionated small resting B cells stimulated with anti‐CD40 monoclonal antibody (mAb), VIP induced IgA1 and IgA2 production without affecting the production of IgG1, IgG2, IgG3, IgG4, IgM, or IgE. When small B cells were separated into sIgA1+, sIgA2+, sIgA1‐ and sIgA2‐ B cells, anti‐CD40 mAb plus VIP induced IgA1 and IgA2 production by surface IgA1‐ (sIgA1‐) and sIgA2‐ B cells, respectively, while having no effect on sIgA1+ and sIgA2+ B cells. This induction by VIP was specific, since anti‐CD40 mAb plus other neuropeptides, i.e., somatostatin or substance P, had no effect, and moreover, the induction was specifically blocked by a VIP antagonist. Further, anti‐CD40 mAb plus various cytokines, including interleukin (IL)‐1β, IL‐2, IL‐3, IL‐4, IL‐5, IL‐6, IL‐10, transforming growth factor‐β, low molecular weight B cell growth factor, and interferon‐γ, did not induce IgA1 and IgA2 production by sIgA1‐ and sIgA2‐ B cells, respectively. These results indicate that in the presence of anti‐CD40 mAb, VIP induces IgA1 and IgA2 production by isotype switching.