bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peripheral deletion of autoreactive CD8+ T cells in transgenic mice expressing H‐2Kb in the liver
Authors: Bertolino Patrick , Heath William R. , Hardy Charles L. , Morahan Grant , Miller Jacques F. A. P. 
Published: March 2007

AbstractThe response of T cells specific for liver antigens was examined in transgenic mice expressing the allogeneic major histocompatibility complex class I molecule H‐2Kb (Kb) under the control of the sheep metallothionein promoter (Met‐Kb mice). To follow the fate of Kb‐specific T cells, and to prevent any aberrant thymic expression of the Kb transgene, the mice were thymectomized, lethally irradiated, protected with bone marrow cells from transgenic mice expressing in their T cells a Kb‐specific T cell receptor identifiable by a clonotypic antibody, and given syngeneic non‐transgenic thymus grafts. Although Kb‐specific CD8+ T cells were produced in the thymus grafts of these manipulated Met‐Kb mice, only small numbers of such cells could be detected in the spleen and lymph nodes. The livers, however, showed signs of damage and were heavily infiltrated by actively dividing CD8+ T cells. We provide strong evidence that the hepatocytes, not generally regarded as antigen‐presenting cells, activated the Kb‐specific CD8+ T cells and that these disappeared after a vigorous autoimmune response that resulted in deletion.
IgD expression on B cells is more efficient than IgM but both receptors are functionally equivalent in up‐regulation CD80/CD86 co‐stimulatory molecules
Authors: Brink Robert , Goodnow Christopher C. , Basten Antony 
Published: March 2007

AbstractThe expression and function of IgM and IgD antigen receptors were studied in a series of anti‐hen egg lysozyme (HEL) immunoglobulin (Ig)‐transgenic mice expressing either IgM alone, IgD alone, or both IgM and IgD. B cell surface expression of IgD was found to be more efficient than that of IgM. Thus antigen receptor density on IgD+, IgM− B cells was twofold higher than on IgM+, IgD− B cells despite the presence of sevenfold lower levels of membrane heavy chain mRNA, and coexpression of IgD with IgM led to almost complete inhibition of surface IgM. In addition, less extensive down‐regulation of IgD occurred following exposure to antigen in vitro. When regulation of CD80/CD86 co‐stimulatory molecules by surface Ig was examined, up‐regulation of the former was initiated at lower antigen concentrations on IgM−, IgD+ compared to IgM+, IgD− B cells. On correcting for antigen receptor density, however, induction of CD80/CD86 by IgM and IgD was comparable. Taken together, these results reinforced the functional similarity of IgM and IgD antigen receptors while at the same time revealing differences in expression which may explain their simultaneous presence on mature B cells.
Mechanism of enhanced antigen presentation by B cells activated with anti‐μ plus interferon‐γ: Role of B7‐2 in the activation of naive and memory CD4+ T cells
Authors: Morokata Tatsuaki , Kato Takuma , Igarashi Osamu , Nariuchi Hideo 
Published: March 2007

AbstractB cells activated with anti‐γ antibody plus interferon (IFN)‐γ exerted strong antigen presentation activity for T cell proliferation. The enhanced antigen presentation function was shown to be due to the increase in B7‐2 expression. When B cells were stimulated with anti‐μ, expression of MHC major histocompatibility complex class II, heat‐stable antigen (HSA), ICAM‐1 and B7‐2 was increased. The presence of IFN‐γ further augmented the expression of B7‐2 on anti‐μ‐stimulated B cells. B7‐1 was not expressed on B cells under these conditions. The participation of B7‐2 in the elicitation of the proliferative response of T cells was confirmed by the inclusion of anti‐B7‐2 antibody in cultures. The enhanced expression of either HSA or ICAM‐1 was shown not to play a major role in the increased B cell antigen presentation capacity. The major T cell population responding to this activated B cell antigen presentation was shown to be CD44low naive CD4+ T cells, whereas CD45RBlow memory CD4+ T cells responded only weakly. The difference in proliferative responses between naive and memory CD4+ T cells was explained by the different efficiency in IL‐2 production of these cell populations in response to antigen presentation by B cells activated by anti‐μ plus IFN‐γ. These results suggest that IFN‐γ plays an important role in recruitment of naive T cells for an immune response.
Self and non‐self peptides treat autoimmune encephalomyelitis: T cell anergy or competition for major histocompatibility complex class II binding?
Authors: Gautam Anand M. 
Published: March 2007

AbstractIn susceptible strains of mice, myelin basic protein (MBP) peptide Ac1‐11 induces experimental autoimmune encephalomyelitis (EAE) providing a useful model for human multiple sclerosis. Ac1‐11 binds major histocompatibility complex (MHC) class II molecules AαuAβu. Here, we show that the Ac1‐11 peptide, when administered intraperitoneally in incomplete Freund's adjuvant (IFA) emulsion, can effectively treat Ac1‐11‐induced EAE in mice. Treatment with Ac1‐11/IFA 9 days after initial immunization with Ac1‐11 in complete Freund's adjuvant (CFA) results in a loss of T cell proliferation to MBP Ac1‐11. This lack of T cell proliferation is not due to T cell anergy and is not specific. A similar lack of T cell proliferation and inhibition of EAE is observed when an ovalbumin peptide OVA323–339 or a sperm whale myoglobin peptide SWM110‐121 are used to treat mice immunized with Ac1‐11. Interestingly, we show that previously unresponsive lymph node cells from treated mice respond normally if Ac1‐11 is presented by fresh antigen‐presenting cells taken from normal mice. These results argue that the lack of T cell proliferation and inhibition of EAE is not due to specific T cell anergy as suggested by others. Instead this appears to be due to blocking of MHC class II molecules AαuAβu by the treating peptides.
Activation of human peripheral blood dendritic cells induces the CD86 co‐stimulatory molecule
Authors: McLellan Alexander D. , Starling Gary C. , Williams Lisa A. , Hock Barry D. , Hart Derek N. J. 
Published: March 2007

AbstractMaximal T lymphocyte responses require presentation of antigen by major histocompatibility complex molecules and delivery of one or more co‐stimulatory signals. Interaction of the CD28 molecule on T lymphocytes with its ligands on antigen‐presenting cells (APC) initiates a critical co‐stimulatory pathway inducing T lymphocyte proliferation and cytokine secretion. Dendritic cells (DC) are potent APC for a primary T lymphocyte response and potential CD28/CTLA‐4 ligands on DC are, therefore, of particular functional relevance. In these experiments, the expression and function of the CD28/CTLA‐4 ligands B7.1 (CD80) and B7.2 (CD86) were examined on human blood DC. Resting DC populations directly isolated by immunodepletion of lineage marker‐positive cells lacked cell membrane expression of CD80 and expressed little or no CD86, although CD86, but not CD80 mRNA was detected by reverse transcription‐polymerase chain reaction analysis. In contrast, low‐density DC isolated after culture in vitro strongly expressed CD86 surface protein, but expressed limited or no CD80, although mRNA for both molecules were detected. Short‐term culture of directly isolated DC up‐regulated both CD80 and CD86 expression. Analysis of the kinetics of CD28/CTLA‐4 ligand induction showed that surface CD86 was present within 8 h, whereas CD80 antigen was first detected after 24 h of culture. The functional importance of CD28/CTLA‐4 ligand up‐regulation on DC during T lymphocyte interactions was demonstrated by the ability of both CTLA‐41g and CD86 monoclonal antibodies (mAb), but not CD80 mAb, to block an allogeneic mixed lymphocyte reaction stimulated by DC populations initially negative for CD80 and CD86. These results demonstrate that CD86 is both the earliest and functionally the predominant co‐stimulatory CD28/CTLA‐4 ligand on DC.
Selective killing of T cells by immunotoxins directed at distinct Vβ epitopes of the T cell receptor
Authors: Rigaut Kathleen D. , Scharff Joshua E. , Neville David M. 
Published: March 2007

AbstractThe potency and specificity of anti‐T cell receptor (TcR)‐directed immunotoxins were studied in two T cell leukemia lines, HPB‐ALL and Jurkat, and in primary T cells. Immunoconjugates were synthesized using anti‐CD3ϵ or distinct anti‐Vβ antibodies cross‐linked to CRM9, a binding site‐mutant of diphtheria toxin. All TcR‐expressing cells display the CD3 complex on the plasma membrane. HPB‐ALL cells express the Vβ5 gene product in the β subunit of the TcR, while Jurkat cells express Vβ8. Vβ expression in primary T cells isolated from buffy coats is heterogeneous. Primary T cell populations expressing specific Vβ epitopes in the TcR were generated by plating CD3+ T cells on Vβ‐specific antibody‐coated flasks or by positive immunomagnetic selection. Immunotoxins directed against the invariant CD3ϵ epitope target and kill all T cells. Immunoconjugates targeted at distinct anti‐Vβ epitopes are specific for cells that express the corresponding gene product in the TcR. The results demonstrate the ability of antiTcR‐based immunotoxins selectively to kill T cells with defined Vβ epitopes. These reagents may be clinically useful in disorders mediated by autoreactive T cell populations exhibiting Vβ restriction and in the treatment of clonal TcR‐expressing lymphomas.
Recombinant CD30 ligand and CD40 ligand share common biological activities on Hodgkin and Reed‐Sternberg cells
Authors: Gruss Hans‐Jürgen , Ulrich Dawn , Braddy Steve , Armitage Richard J. , Dower Steven K. 
Published: March 2007

AbstractThe CD30 ligand (CD30L) and CD40L are members of the tumor necrosis factor (TNF) protein superfamily. CD30L and CD40L are mainly expressed as membrane‐bound proteins by activated T cells. CD30L and CD40L are costimulatory for T cell proliferation and activation. Further, CD40L is a critical signal for T cell‐dependent activation of B cells. Primary and cultured Hodgkin and Reed‐Sternberg (H‐RS) cells, the neoplastic component of Hodgkin's disease (HD), express high levels of the counterreceptors CD30 and CD40. We have found that both the recombinant CD30L and CD40L enhanced interleukin (IL)‐6, TNF and lymphotoxin (LT)‐α release from cultured H‐RS cells. In addition, CD40L, but not CD30L, induced IL‐8 secretion. CD30L and CD40L seem to share some redundant biological activities involved in the deregulated secretion of cytokines known to play a central role in the clinical presentation and pathology of HD. Further, CD30L enhanced surface expression of intercellular adhesion molecule‐1 (ICAM‐1/CD54) on cultured H‐RS cells, which is frequently overexpressed on primary H‐RS cells. CD30L‐ and CD40L‐enhanced CD54 surface expression is followed by elevated shedding of CD54, as shown by detection of elevated 82‐kDa soluble (s) CD54 levels in culture supernatants after stimulation with both ligands. CD30L and CD40L share common pleiotropic biological activities on CD30+/CD40+ H‐RS cells and are elements of the cytokine and cell contact‐dependent activation network typical for HD, a tumor of cytokine producing cells.
Analysis of interleukin receptor gene expression in mouse fetal liver by quantitative polymerase chain reaction
Authors: Jia Gui‐Quan , Gutierrez‐Ramos Jose C. 
Published: March 2007

AbstractWe describe a simplified and sensitive polymerase chain reaction (PCR)‐based method for the quantification of low‐abundance RNA for mouse cytokine receptor genes. Accurate quantification is achieved in a two‐step protocol which uses a synthetic RNA as an internal standard. The proper titration of the amount of mRNA molecules is followed by a kinetic analysis which ensures precise measurement. This quantitative PCR method provides a rapid and reliable way to quantify the amount of cytokine receptor mRNA in samples containing as few as 1000 molecules of RNA for a cytokine receptor target gene. We illustrate our approach by quantifying mRNA levels for two families of cytokine receptor genes in the fetal liver and bone marrow of the mouse. Our results reveal early and abundant expression of the genes encoding the signal transducing subunits interleukin‐2 receptor γ and gp130. Their expression seems to precede that of the genes encoding the specific subunits of these interleukin receptor systems.
T cell repertoire and clonal deletion of Mtv superantigen‐reactive T cells in mice lacking CD4 and CD8 molecules
Authors: Penninger Josef M. , Schilham Marco W. , Timms Emma , Wallace Valerie A. , Mak Tak W. 
Published: March 2007

AbstractCD4−CD8− double‐negative T cells constitute a lymphocyte subpopulation within the thymus and peripheral lymphatic organs that express a unique T cell receptor (TCR) repertoire and do not undergo negative selection. To test whether these cells develop as a distinct lineage or due to altered selection in the absence of CD4 and CD8 expression, we analyzed the TCR repertoire in mice lacking both CD4 and CD8 accessory molecules after homologous recombination (CD40/0CD80/0). We show that mature T cells of CD40/0CD80/0 mice express an unbiased diverse TCR Vβ repertoire comparable to wild type mice. In addition, clonal deletion of mouse mammary tumor virus superantigen‐reactive T cells did occur in CD40/0CD80/0 mice. These data show that the intrinsic lack of CD4 and CD8 expression has no effect on the mature TCR repertoire and that clonal deletion of superantigen‐reactive cells is independent of CD4 and CD8 co‐receptors.
IgA production by peritoneal cavity B cells is IL‐6 independent: Implications for intestinal IgA response
Authors: Beagley Kenneth W. , Bao Shisan , Ramsay Alistair J. , Eldridge John H. , Husband Alan J. 
Published: March 2007

AbstractWe have shown previously both in vitro and in vivo that IL‐6 is an important factor for the development of IgA‐producing B cells. However, despite the lack of this cytokine in mice with targeted disruption of the interleukin (IL)‐6 gene (gene knockout mice), a substantial number of IgA‐producing plasma cells occur in their intestinal mucosa. The experiments reported here indicate that there is a population of IgA‐producing B cell precursors originating from the peritoneal cavity, distinguished from conventional Peyer's patch‐derived precursors by their expression of CD5, and that IgA secretion by these cells is IL‐6‐independent. Further, there is an increase in CD5 expression among brightly staining IgA‐producing cells obtained from the intestinal lamina propria of IL‐6 gene‐disrupted mice compared to normal controls. These data suggest an explanation for the persistence of IgA‐producing plasma cells in the intestinal mucosa of IL‐6‐depleted mice and indicate the importance of IL‐6 for development of conventional precursors of IgA‐producing B cells, but not those derived from the peritoneal cavity pool.
Interleukin‐1β converting enzyme in murine Langerhans cells and epidermal‐derived dendritic cell lines
Authors: Ariizumi Kiyoshi , Kitajima Toshiyuki , Bergstresser Paul R. , Takashima Akira 
Published: March 2007

AbstractInterleukin (IL)‐1β plays an essential role in the induction of T cell‐mediated immune responses in skin. Langerhans cells (LC), which constitutively express IL‐1β mRNA, have been assumed to be the primary source of IL‐1β in murine epidermis. The purpose of this study was to determine whether LC express mRNA for the IL‐1β converting enzyme (ICE), a protease that is required for processing pro‐IL‐1β into an active form. Here, we report that both IL‐1β and ICE mRNA are expressed by the Ia+ population (i.e. LC) in murine epidermis. Moreover, murine epidermal‐derived DC lines (XS series) also express both IL‐1β and ICE mRNA, and they secrete relatively large amounts of IL‐1β following lipopolysaccharide (LPS) stimulation. Finally, LPS‐triggered IL‐1β secretion by XS cells is blocked almost completely by the ICE inhibitor acetyl‐Tyr‐Val‐Ala‐Asp‐CH2OC(O)‐[2,6‐(CF3)2]Ph. These results demonstrate that LC are the primary source of IL‐1β within the epidermis, and suggest that the proinflammatory role of IL‐1β may be regulated pharmacologically by ICE inhibitors in vivo.
TAP polymorphism does not influence transport of peptide variants in mice and humans
Authors: Obst Reinhard , Armandola Elena A. , Nijenhuis Marga , Momburg Frank , Hämmerling Günter J. 
Published: March 2007

AbstractThe major histocompatibility complex (MHC)‐encoded transporter associated with antigen processing (TAP) delivers cytosolic peptides to the lumen of the endoplasmic reticulum (ER) for presentation by MHC class I molecules. For the rat, it has been demonstrated that TAP polymorphism results in the selection of different sets of peptides, the nature of the C terminus being of particular importance. Here, we investigated whether TAP polymorphism in mice and humans has functional consequences for transport of peptide sets variable at the C‐terminal residues. Using cell lines of H‐2d, H‐2k, and H‐2dxk haplotype and a panel of human lymphoblastoid cell lines expressing eight different TAP alleles, we detected species‐specific transport patterns, but no significant influence of TAP polymorphism on peptide selection. In addition, peptides with different core sequences were translocated to the same extent by different TAP. These results suggest that a major contribution of human TAP polymorphism to disease progression and autoimmunity is not very likely.
Interleukin‐2 promoter activity in Epstein‐Barr virus‐transformed B lymphocytes is controlled by nuclear factor‐ϰB
Authors: Mouzaki Athanasia , Serfling Edgar , Zubler Rudolf H. 
Published: March 2007

AbstractThe regulation of interleukin (IL)‐2 gene expression has been investigated mainly in T lymphocytes, the predominant producers of IL‐2. However, B cells can also synthesize IL‐2. In the present study we analyzed the control of IL‐2 promoter activity in Epstein‐Barr virus (EBV)‐transformed B cell clones which are capable of secreting IL‐2 at a low level after stimulation with phorbol 12‐myristate 13‐acetate and the Ca2+ ionophore ionomycin. Transient transfections using reporter constructs with multiples of transcription factor binding sites from the IL‐2 promoter [distal nuclear factor (NF)‐AT, proximal NF‐AT, AP‐1/Octamer (UPS) or NF‐ϰB (TCEd) sites] were performed. In EBV‐transformed B clones, the ϰB site exerted the strongest inducible activity; the NF‐AT binding sites showed either no or only weak activity compared to Jurkat T cells. An IL‐2 promoter bearing a defective NF‐ϰB site was completely inactive in EBV‐B cells, white it still had activity in Jurkat T cells. In seven EBV‐B cell clones or lines differing in their capacity to secrete IL‐2, the activity of the IL‐2 promoter correlated well with the status of IL‐2 secretion. Similarly, a human immunodeficiency virus promoter, whose activity is controlled through ϰB factors, was found to be active in the IL‐2‐producing EBV‐B cells, but inactive in the non‐IL‐2‐producing cells. Electrophoretic mobility shift assays using protein extracts from EBV‐B cells and the IL‐2 NF‐ϰB probe revealed the constitutive generation of ϰB complexes in IL‐2‐secreting cells consisting mainly of heterodimeric p50/p65 complexes. A weaker ϰB complex formation and faster‐migrating complexes were detected in non‐IL‐2‐secreting cells. These results demonstrate that the IL‐2 NF‐ϰB site is indispensable for the activity of the IL‐2 promoter in EBV‐transformed B cells, whereas other transcription factors appear to be less important for IL‐2 expression in these cells.
Ligation of HLA class II molecules promotes sensitivity to CD95 (Fas antigen, APO‐1)‐mediated apoptosis
Authors: Yoshino Tadashi , Cao Liu , Nishiuchi Ritsuo , Matsuo Yoshinobu , Yamadori Ichiro , Kondo Eisaku , Teramoto Norihiro , Hayashi Kazuhiko , Takahashi Kiyoshi , Kamikawaji Nobuhiro , Akagi Tadaatsu 
Published: March 2007

AbstractCD95 (Fas antigen/APO‐1) is up‐regulated in activated lymphocytes, and monoclonal antibody (mAb) to CD95 induces apoptosis. HLA class II molecules play a key role in antigen presentation, ligation of which induces signal transduction. We examined 18 lymphoid cell lines (15 B cell and 3 T cell lines) to investigate the effects of ligation of HLA class II molecules on CD95‐mediated apoptosis. All of the five immature B cell lines were sensitive to anti‐CD95 mAb, and ligation of HLA class II molecules promoted CD95‐mediated apoptosis. In seven B‐blastoid cell lines, two Burkitt lines were resistant to anti‐CD95 mAb in spite of high expression of CD95. In three of five non‐Burkitt B‐blastoid lines, CD95‐mediated apoptosis was augmented by treatment with anti‐HLA class II mAb, while the other two lines lacking CD95 were resistant to anti‐CD95 mAb. Three plasmacytic cell lines showed CD95‐mediated apoptosis, but enhancement by anti‐HLA class II mAb was slight in one cell line and was not observed in the other two lines. Out of three HLA class II antigen‐positive T cell lines, CD95‐mediated apoptosis was observed to some degree in one cell line but was not promoted by the treatment with anti‐HLA class II mAb, and the other two cell lines were resistant to anti‐CD95 mAb. Ligation of HLA class II molecules did not alter CD95 expression in the five cell lines examined, except Su‐DHL‐4 originated from a follicular lymphoma, which showed slight up‐regulation. Taken together, ligation of HLA class II molecules apparently promotes CD95‐mediated apoptosis in immature B cells and non‐Burkitt B blasts. These findings highlight the role of HLA class II molecules in CD95‐mediated apoptosis, which may facilitate rapid clearance of functionally useless cells from the immune system and might be involved in negative selection of B cells.
Schistosoma‐specific helper T cell clones from subjects resistant to infection by Schistosoma mansoni are Th0/2
Authors: Couissinier‐Paris Patricia , Dessein Alain J. 
Published: March 2007

AbstractAlthough T helper cells play a critical role in human immunity against schistosomes, the properties of the T lymphocytes that govern resistance and pathogenesis in human schistosomiasis are still poorly defined. This work addresses the question as to whether human resistance to Schistosoma mansoni is associated with a particular T helper subset. Twenty‐eight CD3+, CD4+, CD8− parasite‐specific T cell clones were isolated from three adults with high degree of resistance to infection by S. mansoni. The lymphokine secretion profiles of these clones were determined and compared to those of 21 CD3+, CD4+, CD8− clones with unknown specificity, established from these same subjects in the same cloning experiment. Almost all parasite‐specific clones produced interleukin (IL)‐4 and interferon (IFN)‐γ in large amounts. However, they generally produced more IL‐4 than IFN‐γ; variations in IL‐4/IFN‐γ ratios were accounted for by differences in IFN‐γ production since IL‐4 levels were comparable for the clones from the three subjects. T cell clones of unknown specificity produced significantly less IL‐4 and more IFN‐γ than parasite‐specific T cell clones. Most clones produced IL‐2, and IL‐2 production did not differ between the two types of clones. Parasite‐specific T cell clones from the resistant subjects were compared to specific T cell clones from a sensitized adult from a nonendemic area: T cell clones from this latter subject were the highest IFN‐γ and the lowest IL‐4 producers, compared to those of resistant subjects. Thus, parasite‐specific T cell clones isolated from adults resistant to S. mansoni belong to the Th0 subset and produced more IL‐4 than IFN‐γ (Th0/2), whereas clones of a sensitized adult from a nonendemic area are also Th0, but produce more IFN‐γ than IL‐4 (Th0/1). These results support previous conclusions on the role of IgE in protection against schistosomes in humans, and may indicate that IFN‐γ is required for full protection.