bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stimulation of all T cells bearing Vβ1, Vβ3, Vβ11 and Vβ12 by staphylococcal enterotoxin A
Authors: Takimoto Hiroaki , Yoshikai Yasunobu , Kishihara Kenji , Matsuzaki Goro , Kuga Hiroshi , Otani Tsuyoshi , Nomoto Kikuo 
Published: March 2007

AbstractTo determine the molecular mechanisms of T cell stimulation by staphylococcal enterotoxin A (SEA), we examined the expression of T cell receptor (TcR) Vβ on the T cells from four strains of mice stimulated in vitro with SEA, using flow cytometric analysis for the number of T cells bearing Vβ3, Vβ6, Vβ8, Vβ11 and RNA blotting analysis for the amount of transcripts of Vβ1, Vβ5 and Vβ12. The number of T cell blasts bearing Vβ1, Vβ3, Vβ1 or Vβ12 were increased in the T cell blasts proliferating in vitro in response to SEA in C57BL/6 mice. In AKR/J mice, which contain few Vβ11‐ or Vβ12‐bearing T cells due to a tolerance to the self‐MHC class II IE‐antigens, T cells bearing Vβ1 or Vβ3 responded to SEA. SEA enriched only Vβ1‐bearing T cells in BALB/c mice carrying Mls‐2a which lack Mls‐1a‐reactive Vβ3‐bearing T cells as well as Vβ11‐ and Vβ12‐bearing T cells. In spite of the presence of Vβ1‐bearing T cells, C3H/He T cells exhibited a very low responsiveness to SEA. T cell repertoires skewed by clonal deletion of self‐reactive T cells may in part account for the different sensitivity to SEA among the different strains. A tolerance to SEA can be established in C57BL/6 mice which have been primed i.v. with SEA and treated i.p. with 200 mg/kg of cyclophosphamide 2 days later. All mature T cells bearing Vβ3 or Vβ11 were virtually abolished in the periphery of tolerant mice. These results suggest that most T cells reactive to SEA bear Vβ1, Vβ3, Vβ11 or Vβ12 and that clonal deletion of mature T cells reactive to SEA may account for the cellular mechanisms for cyclophosphamide‐induced tolerance to SEA.
Several epitopes on native human complement C9 are involved in interaction with the C5b‐8 complex and other C9 molecules
Authors: Kontermann Roland , Deppisch Reinhold , Rauterberg Ernst W. 
Published: March 2007

AbstractTen monoclonal antibodies (mAb) against native human C9 exhibiting various inhibitory effects on the hemolytic activity of C9 (Bausback, J., Kontermann, R. and Rauterberg, E. W., Immunobiology 1988. 178: 58) were further analyzed regarding their reactivities with monomeric C9 (mC9), polymerized C9 (pC9), and the non‐lytic SC5b‐9 complex in enzyme‐linked immunosorbent assay and with the membrane attack complex (MAC) generated on rabbit erythrocytes analyzed by flow cytometry. In addition, the inhibitory effects of mAb on zinc‐induced C9 polymerization were investigated. One epitope of the C‐terminal half of C9b exposed on the surface of pC9 and the MAC seems not to participate directly in lytic function or polymerization since no inhibitory effect of the respective mAb was observed. The nine other mAb directed against epitopes of the C9a part exhibit various inhibitory potentials. The mAb inhibit either hemolysis or polymerization, or both processes. Due to the reactivity with the tested antigens the mAb can be divided into two groups. mAb of the first group bind with nearly the same affinity to all four antigens, whereas mAb of the second group react preferentially with mC9 while their affinity to pC9, SC5b‐9 and the MAC is reduced. Comparison of reaction patterns and inhibitory effects strongly suggest that different epitopes on the surface of native C9 are involved in interaction of C9 with C5b‐8 and/or in C9‐C9 interaction. The finding that mAb inhibiting polymerization of C9 in vitro have no inhibitory effect on hemolysis confirms that C9 polymers are no prerequisite for lysis.
Regulation of T helper‐B lymphocyte adhesion through CD4‐HLA class II interaction
Authors: Mazerolles Fabienne , Amblard François , Lumbroso Catherine , Lecomte Olivia , van de Moortele Pierre‐François , Barbat Christiane , Piatier‐Tonneau Dominique , Auffray Charles , Fischer Alain 
Published: March 2007

AbstractAntigen‐independent adhesion of CD4+ T lymphocytes to Epstein‐Barr virus (EBV)‐transformed B cells is mediated by CD2/lymphocyte function‐associated antigen (LFA)‐3 and LFA‐1/intracellular adhesion molecule (ICAM)‐1. Although some anti‐CD4 antibodies block the antigen‐independent adhesion of CD4+ T lymphocytes, the CD4‐HLA class II interaction does not appear to significantly contribute to the forces of cell adhesion since CD4+ T cells equally bind HLA class II+ and HLA class II− mutant B cells. In addition, conjugates formed between CD4+ T cells and HLA class II− B cells remain stable for at least 1 h while CD4+T/HLA class II+ B cell conjugate percentages promptly drop off. Down‐regulation of CD4 or spontaneous low expression of CD4 also results in a persistance of conjugates formed with B cells. The role of the CD4‐HLA class II interaction has been further studied by investigating the inhibitory effect of synthetic 12‐mer peptides analogous to HLA class II and containing the Arg‐Phe‐Asp‐Ser sequence conserved in the β1 domain. These peptides were previously found to inhibit HLA class II‐restricted T cell responses, this sequence being thought to be involved in CD4‐HLA class II interaction. These peptides block conjugate formation of CD4+ resting T cells or clones but not of CD8+ T cells, by interacting with the T cells as shown by preincubation experiments. Down‐regulation of CD4 or spontaneous low expression results in the loss of the inhibitory activity. The peptide‐mediated inhibition is neutralized by a soluble dimeric CD4 molecule. Alteration within the Arg‐Phe‐Asp‐Ser sequence results in a significant loss of inhibition. It is thus proposed that the CD4‐HLA class II interaction negatively regulates antigen‐independent adhesion of T cells, this interaction involving the highly conserved Arg‐Phe‐Asp‐Ser sequence in the HLA class II β1 sequence as a CD4‐binding site.
Presence of intestinal intraepithelial lymphocytes in mice with severe combined immunodeficiency disease
Authors: Croitoru Kenneth , Stead Ron H. , Bienenstock John , Fulop Gabrielle , Harnish Delsworth G. , Shultz Leonard D. , Jeffery Peter K. , Ernst Peter B. 
Published: March 2007

AbstractThe murine intestinal epithelium contains a heterogeneous population of intraepithelial leukocytes (IEL) most of which are granulated, Thy‐1‐CD5−CD8+. In order to assess the lineage relationship of this subgroup of IEL to peripheral T cells, we examined IEL in mice with the severe combined immunodeficiency (scid/scid) mutation, which lack T and B cells in peripheral lymphoid tissues. Electron and light microscopy showed that the intestine from scid/scid mice had granulated IEL similar to IEL in normal C.B‐17 mice. Flow cytometry of isolated IEL stained with monoclonal antibodies against Thy‐1, CD3, CD4, CD5 and CD8 showed that scid/scid mice IEL contained cells with the Thy‐1−CD4−CD5−CD8+ phenotype. Immunohistochemical staining of IEL in tissue sections with antibodies to Thy‐1 and CD8 confirmed that the Thy‐1−CD8+ cells were in the intestinal epithelium. These scid/scid IEL also lacked CD3 expression and mRNA for the Vγ7 V region gene of the γ T cell receptor. We conclude that scid/scid mice contain precursors for IEL that can differentiate into a granulated Thy‐1−CD5−CD8+ IEL in the intestine. The absence of CD8+ peripheral T cells in these mice suggests that these IEL differ from classical T cells in their ability to differentiate and express CD8 and do not require T cell receptor expression for their localization to the intestine.
Induction of interleukin 6 by human and murine recombinant interleukin 1 in mice
Authors: Libert Claude , Brouckaert Peter , Shaw Alan , Fiers Walter 
Published: March 2007

AbstractInterleukin (IL) 6 is a pleistropic cytokine with activities, among others, on immune cells, hematopoietic precursor cells and hepatocytes. We have investigated the kinetics and amplitude of its in vivo induction in mice after injection of four different IL 1 species as well as murine (m) and human (h) tumor necrosis factor (TNF) and bacterial lipopolysaccharide (LPS) using a sensitive bioassay on 7TD1 cells to measure the IL 6 concentrations. Recombinant mIL 1β, administered as a single i.v. injection in mice, induced the appearance of IL 6 in the plasma with peak levels observed after 2 h. A dose‐response correlation was found between serum IL 6 levels and injected IL 1α concentrations at 3 and 8 h after the injection. We then compared the ability of h/mIL 1α, h/mIL 1β, h/mTNF and LPS to induce IL 6 in mice. We found: (a) LPS is the most potent inducer of IL 6; (b) 3 h after injection, the four IL 1 preparations had induced IL 6 levels comparable with the IL 6 levels observed after TNF injection; (c) high doses of mIL 1, α or β, but not hIL 1, resulted in a high IL 6 level persisting for over 8 h. We conclude that IL 1 is a potent inducer of IL 6 in vivo and that no major differences are observed between the four IL 1 preparations, as evaluated at 3 h after the injection. However, mIL 1α and mIL 1β, in contrast to hIL 1α and hIL 1β, induced a sustained IL 6 level over a longer time period. This pattern of prolonged IL 6 induction is even much more pronounced after mTNF injection, but not after hTNF injection.
CD1c as a target recognition structure for human T lymphocytes: Analysis with peripheral blood γ/δ cells
Authors: Faure Florence , Jitsukawa Setsuko , Miossec Christine , Hercend Thierry 
Published: March 2007

AbstractIt has been shown recently that one γ/δ cell line, termed IDP2, derived from a immunodeficient patient recognizes the CD1c molecule on the surface of target cells. In light of these data, we have tested 43 cloned and 11 polyclonal γ/δ cell lines derived from peripheral blood of 19 donors following nonspecific mitogenic stimulation. In this panel, which included lymphocytes expressing various combinations of γ and δ chains, only one clone, termed J2B7, was found to interact with target cells via a CD1c‐dependent recognition pathway. These J2B7 lymphocytes have, like IDP2, a δ chain which results from the frequent V1/J1 rearrangement while they use a distinct Vγ gene segment. The data support the view that the CD1c major histocompatibility complex “class I‐like” gene product does not have a pivotal contribution to the repertoire of peripheral blood γ/δ cells in adult individuals.
Origin and selection of peripheral CD4−CD8− T cells bearing α/β T cell antigen receptors in autoimmune gld mice
Authors: Wadsworth Scott , Yui Katsuyuki , Siegel Richard M. , Tenenholz Drew E. , Hirsch Joshua A. , Greene Mark I. 
Published: March 2007

AbstractWe have analyzed the origin and development of unusual CD4−CD8− α/β T cell receptor‐positive peripheral T cells produced in large numbers by mice homozygous for the gld mutation (C3H‐gld/gld). These mice may be an important model for investigating processes controlling T cell development. Bone marrow transfers demonstrated that the gld defect was intrinsic to bone marrow‐derived cells. Clonal deletion of potentially autoreactive cells was observed in peripheral gld CD4−CD8−, CD4+CD8−, and CD4−CD8+ T cells, as well as mature thymocytes. This suggests that gld CD4−CD8− T cells have passed through the thymus in ontogeny and that gld autoimmunity does not result from a general defect in elimination of self‐reactive thymocytes. These observations, combined with demethylation of the CD8 gene in the CD4−CD8− population, support prior expression of CD4 and/or CD8 in gld CD4−CD8− T cell ontogeny, perhaps at a CD4+CD8+ stage. Steroid sensitivity of gld thymocytes and CD4−CD8− T cells was normal. Therefore, we found no gross abnormalities in two major mechanisms of inducible cell death in the gld thymus, the clonal deletion process associated with tolerance and the steroid‐inducible endogenous endonuclease thought to be involved in apoptosis of unselected thymocytes. The data suggest that if gld CD4−CD8− T cells arise via escape from normal elimination in the thymus, they must do so by a novel defect in thymic selection (perhaps related to aberrant positive signals) and/or are expanded by an extrathymic process which allows clonal deletion to occur.
Regulation of interleukin 1 generation in immune‐activated fibroblasts
Authors: Huleihel Mahmoud , Douvdevani Amos , Segal Shraga , Apte Ron N. 
Published: March 2007

AbstractIn the present study we have demonstrated that fibroblasts can generate the inflammatory cytokine interleukin 1 (IL 1) under conditions similar to those abundant in cellular immune responses. Thus, induction of IL 1 requires a sequential two‐step protocol which consists of preactivation of mouse embryo fibroblasts (MEF) with crude preparations of T cell or macrophage‐derived conditioned media (CM; 72 h), followed by a challenge with lipopolysaccharide (LPS; 24 h). Unstimulated fibroblasts or such cells activated by either CM or LPS produced only low levels of IL 1, while a synergism between both signals was observed for obtaining maximal IL 1‐like activity in MEF. Each of a series of individual recombinant lymphokines and cytokines (IL 2, granulocyte/macrophage‐colony‐stimulating factor, tumor necrosis factor, IL 1β and interferons‐α, β and γ) was shown to serve as an efficient priming signal for the induction of IL 1. IL 1‐like activity in fibroblasts was detected in cell lysates or associated with the producing‐cell membrane but not in culture fluids. Immune‐stimulated fibroblasts, activated under such experimental conditions, were shown to actively transcribe mRNA of both IL 1 genes (α and β). For the expression of IL 1‐specific mRNA in fibroblasts a single stimulus, provided by either LPS or a lymphokine/cytokine, was sufficient; however, a more intense signal was observed when both stimuli were applied. The IL 1‐like biological activity of fibroblast origin was significantly reduced by anti‐IL 1α antibodies. Thus, fibroblasts, when activated by immune and bacterial products, generate IL 1 which in turn possibly amplifies cellular immune responses or inflammatory processes in connective tissues.
Variable region sequences of pathogenic anti‐mouse red blood cell autoantibodies from autoimmune NZB mice
Authors: Reininger Luc , Shibata Takanori , Ozaki Shoichi , Shirai Toshikazu , Jaton Jean‐Claude , Izui Shozo 
Published: March 2007

AbstractNew Zealand Black (NZB) mice spontaneously develop a severe autoimmune hemolytic anemia due to the production of anti‐mouse red blood cell (MRBC) autoantibodies. The contribution of variable region genes and somatic mutations in the pathogenicity of anti‐MRBC autoantibodies was investigated by mRNA sequencing of eight NZB anti‐MRBC monoclonal autoantibodies, among which five are capable of inducing anemia in BALB/c mice. Here we report that at least three VH gene families (J558, J606 and 3609) and five Vϰ, subgroups (Vϰ8, 9, 19, 21 and 28), in combination with several D, JH and Jϰ, gene segments, encode anti‐MRBC autoantibodies. Thus, the NZB anti‐MRBC autoantibodies, whether pathogenic or not, are encoded by a large number of immunoglobulin gene elements and by members of known VH and Vϰ, gene families with preferential usage of VH gene families most distal to the D regions. The presence of several mutations in the JH gene segments of both IgM and IgG anti‐MRBC autoantibodies, whether pathogenic or not, strongly suggests that their VH regions may be highly mutated and that the mechanism of somatic diversification might be important in the generation of anti‐MRBC autoantibodies. Our results support the idea that anti‐MRBC autoimmune responses are likely to be generated by an antigen‐driven mechanism.
Identification of a bovine surface antigen uniquely expressed on CD4−CD8− T cell receptor γ/δ+ T lymphocytes
Authors: Clevers Hans , Machugh Niall D. , Bensaid Albert , Dunlap Sabrina , Baldwin Cynthia L. , Kaushal Anita , Iams Keith , Howard Christopher J. , Ivan Morrison W. 
Published: March 2007

AbstractIn this study, two monoclonal antibodies, IL‐A29 and CC15, are described that identify a novel bovine cell surface marker of 215/300 kDa. The antibodies reacted with a discrete population of resting lymphocytes in peripheral blood which, in young animals, constituted about 25% of the mononuclear cells. Thymus, lymph nodes and spleen contained < 5% positive cells. These cells were negative for surface Ig, a monocyte/granulocyte marker, and the T lymphocyte antigens CD2, CD6, CD4 and CD8. Immunohistological analyses revealed the presence of IL‐A29/CC15‐positive lymphocytes in the thymic medulla, in the outer cortex of lymph nodes, in the marginal zones of the spleen, in the dermal and epidermal layers of the skin and in the lamina propria of the gut. The IL‐A29/CC15+ cells in unfractionated blood mononuclear cells responded in autologous and allogeneic mixed lymphocyte cultures, and when purified they responded to concanavalin A in the presence of recombinant interleukin 2. These observations suggested this population of cells belonged to the T cell lineage. In order to unambiguously define their lineage, cDNA clones encoding bovine T cell receptor (TcR) and CD3 proteins were isolated. Northern blot analyses of IL‐A29/CC15+ cell populations and of established cell lines of various lineages demonstrated that they expressed TcR δ and CD3γ, δ and ϵ mRNA; TcR α was not expressed, whereas only a truncated form of TcR β mRNA was present. These results indicate that the IL‐A29 and CC15 antibodies define a unique population of CD4−CD8−, γ/δ T cells.
New B cell epitopes in the Plasmodium falciparum malaria circumsporozoite protein
Authors: Stüber Dietrich , Bannwarth Wilhelm , Pink J. Richard L. , Meloen Rob H. , Matile Hugues 
Published: March 2007

AbstractMost antibodies directed against the Plasmodium falciparum circumsporozoite (CS) protein react with its central domain, which contains about 40 repeats of the tetrapeptide Asn‐Ala‐Asn‐Pro (NANP). To search for new epitopes in the non‐repetitive part of the CS protein, we expressed the non‐repetitive regions of the protein in E. coli as fusion proteins with mouse dihydrofolate reductase linked to six adjacent histidine residues. These fusion proteins were obtained at > 70% purity by a single Ni‐chelate affinity chromatography step. Of the new epitopes defined in the C‐terminal portion of the CS protein, three are located in a stretch of 65 amino acids immediately C‐terminal of the protein's central repetitive domain. Pooled sera from inhabitants of a malaria‐endemic area reacted with epitopes in this region of the molecule, and four mouse monoclonal antibodies to this region also reacted with the native CS protein on sporozoites. Two of the monoclonal antibodies reacted with a peptide PNDPNRNVD derived from a conserved region of the CS protein. The other two antibodies showed different reactivities to sporozoites of the NF54 and Ro59 parasite isolates. One, which reacted with a peptide ENANANNAV, recognized Ro59 but not NF54 sporozoites, while the other reacted with a small percentage of NF54 but not Ro59 sporozoites. Antibodies which react with non‐repetitive regions of the CS protein could contribute to maintaining its genetic variability.
Selective expansion of a specific anti‐tumor CD8+ cytotoxic T lymphocyte clone in the bulk culture of tumor‐infiltrating lymphocytes from a melanoma patient: Cytotoxic activity and T cell receptor gene rearrangements
Authors: Gervois Nadine , Heuze Françoise , Diez Elisabeth , Jotereau Francine 
Published: March 2007

AbstractIn vitro culture of metastatic melanoma fragments with 150 units of recombinant interleukin 2 resulted in the successive expansion of CD4+ and then CD8+ tumor‐infiltrating lymphocytes (TIL) throughout a 2‐month period. TIL cultured for 43 days and consisting of 95% CD8+ and 10% CD4+ T lymphocytes were cloned by limiting dilution (LD). Thirteen CD8+ and thirty‐one CD4+ clones were obtained, indicating that the frequency of clonogenic CD8+ proliferative T lymphocytes was much lower than that of their CD4+ homologues. When LD was performed in the presence of autologous melanoma cells the frequency of CD8+ clones was increased by factor 4. The DNA from TIL of day 43 bulk culture and of six CD8+ clones was hybridized with T cell receptor (TcR) β and γ probes. Identical configuration of the nonfunctional γ and functional β TcR genes was found in “bulk culture” and cloned TIL. The CD8+ clones therefore derived from a clonal population of CD8+ cells which had expanded in vitro before the LD.All the CD8+ clones tested were strongly cytotoxic for autologous melanoma cells but did not kill autologous fibroblasts or concanavalin A blasts, or any of the 10 allogeneic tumor targets tested, including 5 melanomas, 2 breast cell lines, 1 neuroblastoma, K‐562 and the Epstein‐Barr virus‐transformed cell line used as a feeder. Furthermore, specific killing was inhibited by monoclonal antibodies against CD3, CD8, TcR α/β and against class I major histocompatibility complex antigens indicating that these cytotoxic T lymphocyte clones recognized autologous tumor cells through the TcR, in an HLA class I‐restricted manner. These data show that it is feasible to obtain tumor‐specific cytotoxic T lymphocytes from melanoma TIL with a simple culture technique and that a single clone could be expanded to more than 1010 cells which should allow testing of immunotherapeutic potential of these cells by adoptive transfer into melanoma patients.
Immunoglobulin‐specific T‐B cell interaction III. B cell activation by immunoglobulinrecognizing T cell clones
Authors: Mazel Svetlana M. , Rudensky Alexander Y. , Yurin Vitalij L. 
Published: March 2007

AbstractImmunoglobulin (Ig)‐specific T‐B cell interactions were studied in the model of T cell recognition of Ig ϰ chain Igϰ‐1b allotype in Igϰ‐1‐congenic rats. Using Igϰ‐1b‐recognizing major histocompatibility complex (MHC)‐restricted T helper clones from August rats we have shown that Igϰ‐1b+ B cells from congenic August. 1b rats presented Igϰ‐1b epitope of the processed self‐synthesized Ig to T clones. This interaction was found to be a bidirectional regulatory event inducing specific MHC‐dependent proliferation of both interacting T cell and B cell as well as Ig(Igϰ‐1b) synthesis. Small Igϰ‐1b+ B cells were capable of inducing T clone proliferation and becoming activated in response to the same T clone. Limiting dilution analysis suggested that every tenth cell in Igϰ‐1b+ B cell population is involved in this interaction. The bystander activation of Igϰ‐1a+ B cells by T clones in the presence of irradiated Igϰ‐1b+ spleen cells, if observed, was less than the level of specific Igϰ‐1b+ B cell proliferation. In contrast to a 20‐fold increase of Ig(Igϰ‐1b) levels upon stimulation of Igϰ‐1b+/1a+ B cell population from heterozygous (August × August.1b)F1 rats by T clones, a “nonspecific” increase of Ig(Igϰ‐1a) was not observed. This result demonstrates the requirement for direct T‐B contact for B cell activation to occur. The data suggest a great functional potency of T‐B interactions mediated by T cell recognition of Ig‐derived peptide/MHC class II complexes on the B cell surface. The implication of the data for idiotypic regulation enables us to propose the existence of putative idiopeptidic network T‐B cell interactions.