bluuebunny/crossref_metadata_2025_split huggingface dataset:
A myelin oligodendrocyte glycoprotein peptide induces typical chronic experimental autoimmune encephalomyelitis in H‐2b mice: Fine specificity and T cell receptor Vβ expression of encephalitogenic T cells
Authors: Mendel Itzhack , de Rosbo Nicole Kerlero , Ben‐Nun Avraham 
Published: March 2007

AbstractA predominant response to myelin oligodendrocyte glycoprotein (MOG) was recently observed in patients with multiple sclerosis (MS). To study the possible pathogenic role of T cell response to MOG in MS, we have investigated the encephalitogenic potential of MOG. Synthetic MOG peptides, pMOG 1‐21, 35–55, 67–87, 104–117 and 202–218, representing predicted T cell epitopes, were injected into C57BL/6J and C3H.SW (H‐2b) mice. The mice developed significant specific T cell responses to pMOG 1–21, pMOG 35–55 and pMOG 104–117. However, pMOG 35–55 was the only MOG peptide which could induce neurological impairment. The highly reproducible disease was chronic, with ascending paralysis and neuropathology comparable with those observed in experimental autoimmune encephalomyelitis (EAE) induced by myelin basic protein or proteolipid protein, except that in H‐2b mice the disease was consistently non‐remitting. These features differ markedly from those which we recently observed in PL (H‐2u) mice with pMOG 35–55‐induced disease. In PL mice, pMOG 35–55‐induces atypical chronic relapsing EAE, the expression and progression of which are unpredictable. Hence, in different mouse strains, the same MOG peptide can induce typical EAE characterized by ascending paralysis, or atypical EAE with unpredictable clinical signs. pMOG 35–55‐specific T cells from H‐2b mice recognized an epitope within amino acids 40–55 of the MOG molecule, and pMOG 40–55‐reactive T cell lines were encephalitogenic upon transfer into syngeneic recipients. The encephalitogenic pMOG 35–55‐reactive C57BL/6J T cell lines expressed Vβ1, Vβ6, Vβ8, Vβ14 and Vβ15 gene segments, and the pMOG 35–55‐reactive C3H.SW T cell lines expressed Vβ1, Vβ2, Vβ6, Vβ8, Vβ10, Vβ14, and Vβ15 gene segments. However, in both mouse strains, the utilization of the Vβ8 gene product was predominant (40–43 %). The highly reproducible encephalitogenic activity of pMOG 35–55 strongly suggests a pathogenic role for T cell reactivity to MOG in MS and supports the possibility that MOG may also be a primary target antigen in the disease.
Restriction of self‐antigen presentation to cytolytic T lymphocytes by mouse peptide pumps
Authors: Gournier Héène , Pascolo Steve , Siegrist Claire‐Anne , Jehan Josette , Pérarnau Béatrice , Garcia Zacarias , Rose Thierry , Neefjes Jacques , Lemonnier François A. 
Published: March 2007

AbstractTransport of an immunogenic self‐peptide from the second domain of the mouse major histocompatibility complex (MHC) H‐2Kd class I molecule is blocked at the TAP1‐TAP2 peptide pump level due to its amino acid sequence and is not presented to cytolytic T lymphocytes (CTL). We demonstrate that first, TAP1‐TAP2 pumps can restrict antigen presentation by selecting against internal peptide motifs which are not involved in peptide binding to MHC class I molecules. Second, some molecules targeted to the endoplasmic reticulum are processed for MHC class I presentation in the cytosol. Third, some abundantly expressed immunogenic self‐peptides are cytosolically sequestered. The advantage for the host, in terms of the peripheral T cell repertoire is that the spared CTL can be used to recognize foreign antigens. It is, however, anticipated that this advantage will be exploited by pathogens to evade immune surveillance by similar strategies.
A point mutation in the human CD45 gene associated with defective splicing of exon A
Authors: Thude Hansjörg , Hundrieser Joachim , Wonigeit Kurt , Schwinzer Reinhard 
Published: March 2007

AbstractCD45 is a receptor‐type protein tyrosine phosphatase involved in the regulation of lymphocyte activation. Different CD45 isoforms are generated by alternative splicing of three variable exons (A, B and C). The pattern of CD45 splicing depends upon cell type and state of activation. CD45RA isoforms (containing exon A‐encoded sequences) can usually be found on a subset of resting T cells, but not on activated T cells. We have recently described a variant pattern of CD45RA expression which is characterized by continuous expression of CD45RA molecules on activated and memory T cells. Here, we demonstrate that this phenotype is associated with heterozygosity for a point mutation at nucleotide position 77 of exon A, leading to a C → G transition. This mutation does not change the protein sequence of the CD45RA isoform. We conclude that position 77 is part of a motif necessary for splicing of exon A, which supports the hypothesis that sequences within exons have significant effects on alternative splicing. The mutation of this motif might prevent binding of a transacting splice factor. In the heterozygous state, this mutation is not associated with impaired T cell reactivity. Functional consequences of the homozygous state remain to be elucidated.
Macrophages, but not dendritic cells, present collagen to T cells
Authors: Michaëlssony Erik , Holmdahl Meirav , Engström Åke , Burkhardt Harald , Scheynius Annika , Holmdahl Rikard 
Published: March 2007

AbstractDendritic cells, such as epidermal Langerhans cells, play a crucial role for the antigen‐specific priming of T cells. We have addressed the question whether dendritic cells present collagen, a major protein component in tissues through which dendritic cells migrate, i.e. the basement membrane, dermis, and synovial tissue. Langerhans cells, spleen cells and peritoneal macrophages were compared for antigen‐presenting capacity using a panel of mouse T cell hybridomas reactive with different determinants on type II collagen, myelin basic protein, ovalbumin and pepsin. Langerhans cells did not present any of the type II collagen determinants, unless the antigen was administered as a 15‐mer peptide, but did present myelin basic protein, ovalbumin and pepsin. Spleen cells and peritoneal macrophages, in contrast, presented all type II collagen determinants. This biased antigen presentation was also observed when Langerhans cells were pulsed with antigen in vivo. The inability to present type II collagen is related to the collagen sequence as such, since both native type II collagen, type II collagen α chains, as well as a type II collagen determinant incorporated in type I collagen, were not presented by Langerhans cells. In addition, granulocyte/macrophage colony‐stimulating factor‐expanded blood dendritic cells displayed the same biased antigen presentation, suggesting that the inability to present collagen is not restricted to dendritic cells localized in epidermis. B cell‐deficient mice could prime a type II collagen‐reactive T cell response, thus excluding B cells as obligatory antigen‐presenting cells for the priming of collagen‐reactive T cells. We suggest that neither Langerhans cells nor B cells, but macrophages are the primary antigen‐presenting cells in the immune response towards type II collagen.
Local Fas/APO‐1 (CD95) ligand‐mediated tumor cell killing in vivo
Authors: Rensing‐Ehl Anne , Frei Karl , Flury Renata , Matiba Bernd , Mariani Sara M. , Weller Michael , Aebischer Patrick , Krammer Peter H. , Fontana Adriano 
Published: March 2007

AbstractFas/APO‐1 (CD95) is a cell surface receptor which mediates apoptosis when ligated by specific antibodies or by its recently cloned natural ligand, FasL. We have studied the cytotoxic potential of FasL in vivo using Fas/APO‐1‐expressing Yac‐1 cells as targets. Supernatant harvested from Neuro‐2a cells transfected with the murine FasL cDNA contains FasL and transduces a potent apoptotic signal to Yac‐1 cells in vitro. Specificity of FasL‐mediated cytotoxicity was confirmed by competition assays using soluble Fas or anti‐Fas/APO‐1 F(ab')2 fragments which specifically interfere with FasL‐Fas/APO‐1 interactions. Intraperitoneal injection of FasL‐containing supernatant efficiently killed Yac‐1 target cells which had been implanted in capsules into the peritoneal cavity of mice. Analysis of the target cells revealed DNA fragmentation and nuclear changes typical of apoptosis. As previously shown, intraperitoneal injection of anti‐Fas/APO‐1 antibodies caused liver failure (Ogasawara, J., Watanabe, F. R., Adachi, M., Matsuzawa, A., Kasugai, T., Kitamura, Y., Itoh, N., Suda, T. and Nagata, S., Nature 1993. 364: 806) and was observed at doses which did not reduce Yac‐1 cell viability. In contrast, FasL did not induce histopathology in the liver when applied intraperitoneally at doses cytotoxic for Yac‐1 cells. However, intravenous administration of FasL induced lethal liver hemorrhages and hepatocyte apoptosis. Thus, locally applied FasL kills tumor cells very efficiently without systemic toxicity and may therefore represent a candidate for local tumor treatment.
Macrophages regulate induction of delayed‐type hypersensitivity and experimental allergic encephalomyelitis in SJL mice
Authors: Cua Daniel J. , Hinton David R. , Kirkman Linda , Stohlman Stephen A. 
Published: March 2007

AbstractThe relationship between the delayed‐type hypersensitivity (DTH) response and susceptibility to experimental allergic encephalomyelitis (EAE) was examined using a unique age‐dependent defect in the DTH response in an EAE‐susceptible mouse strain. Young adult male SJL mice (< 10 weeks of age) are defective in DTH responses following immunization with a variety of soluble antigens. By contrast, they respond to antigens applied to the skin, demonstrating a normal contact sensitivity response. In this report, we show that the nonresponder male SJL are also unable to mount a DTH response to soluble neuroantigens or neuroantigens emulsified in complete adjuvant, and are additionally resistant to actively induced EAE. This contrasts with the DTH response in older males (> 10 weeks of age) and young adult females (6 weeks of age), which are both DTH responders and susceptible to EAE. By contrast, all three groups are susceptible to EAE mediated by the transfer of activated effector T cells, suggesting that the defect in young adult males is in the induction of effectors. Furthermore, transfer of a macrophage population from female responders to young male non‐responders mediates the induction of both DTH responsiveness and EAE susceptibility. The phenotype of this antigen‐presenting cell is (I‐A+, Mac‐1+, Mac‐2−, Mac‐3+), identical to the phenotype of the macrophage regulating DTH responsiveness in this strain of mice. These data are consistent with the hypothesis that a defect in this cell inhibits induction of both CD4+ Th1 DTH and EAE effector T cells.
Regulatory T cells in thymic epithelium‐induced tolerance. I. Suppression of mature peripheral non‐tolerant T cells
Authors: Modigliani Yves , Pereira Pablo , Thomas‐Vaslin VÉRonique , Salaün Josselyne , Burlen‐Defranoux Odile , Coutinho Antonio , Douarin Nicole Le , Bandeira Antonio 
Published: March 2007

AbstractAthymic mice grafted at birth with allogeneic thymic epithelium (TE) display life‐long tolerance to tissue grafts of the TE donor strain, in spite of harboring peripheral T cells capable of rejecting those grafts. Tolerance is maintained in these chimeras by TE‐specific regulatory CD4 T cells. We presently address the quantification and the mechanisms of this dominant tolerance process. C57BL/6 mice containing variable but defined numbers of peripheral, resident T cells received cell transfers of graded numbers of peripheral T cells from B6(BALB E10) chimeras (C57BL/6 nude mice grafted with TE from 10‐day‐old BALB/c embryos), resulting in a series of animals containing a wide range of donor (tolerant) versus host (non‐tolerant) T cell chimerism. Increasing the relative representation of donor T cells results in a progressive delay in the rejection of BALB/c skin grafts, life‐long tolerance being achieved at a ratio of tolerant and non‐tolerant T cell populations of 1. In recipients displaying full tolerance, graftreactive non‐tolerant T cells were not deleted, anergized or committed to noninflammatory functions. Thus, sorted host T cells from tolerant recipients readily rejected BALB/c skin grafts upon transfer to immunodeficient animals. Finally, measurements of “helper” and inflammatory activities, as well as interleukin‐4 and interferon‐γ production, failed to discriminate between T cell populations from tolerant and non‐tolerant animals after specific in vitro stimulation. We conclude that: (a) TE‐selected regulatory T cells can suppress, in a quantitative manner, in vivo T cell responses against major and minor histocompatibility antigens expressed by the TE and, (b) this suppressive activity neither inactivates mature non‐tolerant T cells, nor does it seem to drive their differentiation along noninflammatory pathways.
Expression of a gastric autoantigen in pancreatic islets results in non‐destructive insulitis after neonatal thymectomy
Authors: Barrett Simon P. , Van Driel Ian R. , Tan Seong‐Seng , Alderuccio Frank , Toh Ban‐Hock , Gleeson Paul A. 
Published: March 2007

AbstractAutoimmune gastritis, induced by day‐3 thymectomy of BALB/c mice, is a destructive CD4+T cell‐mediated disease characterized by leukocyte infiltrates in the gastric mucosa, loss of parietal and chief cells and anti‐gastric H/K ATPase autoantibodies. Our previous studies have indicated that a T cell response to the H/K ATPase β subunit is required for the onset of autoimmune gastritis (Alderuccio, F., Toh, B. H., Tan, S. S., Gleeson, P. A. and van Driel, I. R.,J. Exp. Med.1993.178:419). To determine whether a response to the β subunit autoantigen is alone sufficient to induce autoimmunity, or whether other tissue‐specific factors are required, we have generated transgenic mice expressing the gastric H/K ATPase β subunit in β islet cells of the pancreas (RIP‐H/Kβ). RIP‐H/Kβ mice developed autoimmune gastritis and insulitis after day‐3 thymectomy. Significantly, insulitis, observed as a peri‐islet infiltrate, was only detected in thymectomized mice with autoimmune gastritis. There was no apparent immune destruction of the pancreas as insulitis did not progress to invasion of the islets or diabetes. Double transgenic mice, expressing the gastric H/K ATPase β subunit in the thymus and in the pancreas, were protected from both gastritis and insulitis after day‐3 thymectomy. Therefore, insulitis in the RIP‐H/Kβ mice appears to be dependent on a T cell response to the H/K ATPase β subunit. This is the first example where an organ‐specific initiating autoantigen has been expressed in another peripheral tissue. Autoimmune destruction in the stomach, but not the pancreas, indicates that tissue‐specific factors play a fundamental role in the development of organ‐specific autoimmunity.
CD4/major histocompatibility complex class II interaction analyzed with CD4‐ and lymphocyte activation gene‐3 (LAG‐3)‐Ig fusion proteins
Authors: Huard Bertrand , Prigent Philippe , Tournier Muriel , Bruniquel Denis , Triebel Frédéric 
Published: March 2007

AbstractWe analyzed CD4 major histocompatibility complex (MHC) class II interactions with CD4 and lymphocyte activation gene (LAG)‐3 recombinant fusion proteins termed CD4Ig and LAG‐3Ig. CD4Ig bound MHC class II molecules expressed on the cell surface only when used in the micromolar range. This weak CD4Ig binding was specific, since it was inhibited by anti‐CD4 and anti‐MHC class II mAb. LAG‐3Ig bound MHC class II molecules with intermediate avidity (Kd = 60 nM at 37°C). Using LAG‐3Ig as a competitor in a CD4/MHC class II‐dependent cellular adhesion assay, we showed that this recombinant molecule was able to block CD4/MHC class II interaction. In contrast, no inhibition was observed in a CD4/MHC class II‐dependent T cell cytotoxicity assay. Together, these results suggest that co‐engagement of the TcR with CD4 alters the CD4/MHC class II molecular interaction to become insensitive to LAG‐3Ig competition.
The VDJ repertoire expressed in human preB cells reflects the selection of bona fide heavy chains
Authors: Milili Michèle , Schiff Claudine , Fougereau Michel , Tonnelle Cécile 
Published: March 2007

AbstractIn early steps of B cell differentiation, μ chains are transiently expressed in association with a surrogate light chain (ΨL) composed of the λ‐like and VpreB monomorphic polypeptides, thus forming a putative preB receptor. Using a monoclonal anti‐VpreB antibody, preB cells were isolated from two adult human bone marrow samples and their VDJ repertoire analyzed at the transcription level. All VH families were identified and further analysis focused on VH3 sequence analysis of 37 distinct VDJ cDNA clones. The VH3 genes expressed in the two bone marrow samples were also encountered in fetal liver and adult peripheral blood lymphocytes with a roughly similar contribution of 3.30, 3.23, 3.9 and 3.53. The characteristic features of the preB repertoire as compared to the activation B repertoire include the quasi absence of somatic mutations, limited N diversity and a shorter third complementarity‐determining region (CDR3). It also significantly differs from the fetal repertoire, which makes higher usage of DQ52 and has CDR3 of even shorter lengths. The almost constant presence of glycine residues in the CDR3 and predominance of JH4 with a low level of DQ52 DH usage, suggest that preB cell clones are submitted to an initial selective pressure which should be antigen independent. The bona fide heavy chains would be merely selected for their ability to interact with the surrogate light chains, thus shaping the repertoire that will be co‐expressed with immunoglobulin light chains in IgM molecules.
Nerve growth‐factor and anti‐CD40 provide opposite signals for the production of IgE in interleukin‐4‐treated lymphocytes
Authors: Brodie Chaya , Oshiba Akihiro , Renz Harald , Bradley Katherine , Gelfand Erwin W. 
Published: March 2007

AbstractNerve growth factor (NGF) is a well‐known neurotrophic factor acting on both the peripheral and the central nervous systems. In addition, it has been shown to play a role in the function of the immune system through specific receptors. Both high‐affinity and low‐affinity NGF receptors (NGFR) are expressed on human B lymphocytes. The low‐affinity NGFR has been shown to have structural homology with another specific B cell surface molecule, CD40, which plays an important role in IgE production. In view of the structural similarities of the p75 NGFR and CD40 we examined whether NGF may also be involved in the regulation of IgE production. We found that NGF and anti‐CD40 exerted opposite effects on the induction of IgE by IL‐4 in peripheral blood mononuclear cells. NGF inhibited the induction of IgE by IL‐4 and this inhibition was not mediated through blocking of the induction of CD23 nor through inhibition of IL‐4R expression. The inhibition of IL‐4‐dependent IgE production was observed on surface (s)IgE+ and sIgE−/sIgM+ B lymphocytes. Anti‐CD40 on the other hand, exerted an enhancing effect on IgE production and its addition to IL‐4 provided a signal that was resistant to the inhibitory effect of NGF. Antagonistic effects of NGF and IL‐4 were also observed for other Ig isotypes since IL‐4 prevented the increase in IgA and IgM production induced by NGF. These data indicate that although NGFR and CD40 belong to the same receptor super‐family and exert similar proliferative effects on B lymphocytes, they interact differently with IL‐4 in the regulation of IgE production.
Activation via the antigen receptor is impaired in T cells, but not in B cells from patients with common variable immunodeficiency
Authors: Fischer Michael B. , Wolf Hermann M. , Hauber Ilona , Eggenbauer Heinz , Thon Vojtech , Sasgary Maria , Eibl Martha M. 
Published: March 2007

AbstractThe patients included in this study belong to a subset of common variabie immunodeficiency (CVID) patients whose peripheral blood T cells have a T cell receptor (TCR)‐mediated activation defect leading to impaired expression of the interleukin (IL)‐2 gene upon stimulation with recall antigens (tetanus toxoid, Escherichia coli) or superantigens (staphylococcal enterotoxins). In the present report we demonstrate that the patients' peripheral blood T cells failed to generate the second messenger inositol 1,4,5‐trisphosphate (Ins(1,4,5)P3) following stimulation with superantigen or mAb specific for the monomorphic region of the TCR β‐chain. Patients' T cell lines were also impaired in generating Ins(1,4,5)P3 when stimulated with tetanus toxoid‐pulsed autologous monocytes. Addition of a second or third co‐stimulatory signal provided by recombinant IL‐2, CD28 or both had no effect on the Ins(1,4,5)P3 formation of the patients' antigen‐driven T cell lines. The T cell activation defect, however, was not absolute, as Ins(1,4,5)P3 formation in the patients' T cells after phytohemagglutinin or aluminium fluoride stimulation was normal. The impairment in signal transduction via the T cell antigen receptor was limited to the patients' T cells, as no activation defect after ligation of surface immunoglobulin, the antigen receptor on B cells, could be detected.
Divergent evolution in the mechanisms controlling major histocompatibility complex class II gene transcription in mouse and human
Authors: De Lerma Barbaro Andrea , Rigaud Gildas , Sartoris Silvia , Nicolis Morena , Cestari Tiziana , Accolla Roberto S. 
Published: March 2007

AbstractThe expression of the major histocompatibility complex (MHC) class II gene family is developmentally regulated and, in general, in a coordinate manner. In this study, we show that the expression of the entire repertoire of human class II genes, otherwise transcriptionally silent in the bare lymphocyte syndrome‐derived BLS1 cell line, can be rescued by somatic cell hybridization with normal mouse spleen cells. The analysis of the interspecies cell hybrids revealed a particularly important and unprecedented aspect. A return to the BLS1‐like, human MHC class II‐negative phenotype due to segregation of mouse chromosomes was accompanied in certain hybrids by loss of IE, but not IA cell surface antigen expression. At the molecular level, this was the result of lack of Eα‐specific mRNA in the presence of Eβ‐, Aα‐ and Aβ‐specific mRNA. Thus, the mouse trans‐acting function operating across species barriers and able to complement the defect of human BLS1 cells diverged in mice to control Ea, but not Eb, Aa and Ab gene expression. These findings suggest that evolutionary pressure has maintained the expression of the MHC class II multigene family under the control of quite distinct species‐specific transcriptional mechanisms.