bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid killing of murine lymph node T blasts by intestinal intraepithelial lymphocytes in vitro
Authors: Kawamoto Yasuko , Sasaki Keiko , Kato Yutaka , Kojima Keisuke , Tsuji Takao , Miyama Akio 
Published: March 2007

AbstractWe examined the effect of murine intestinal intraepithelial lymphocytes (IEL) on the proliferation of murine lymph node T cells (LN‐T) in vitro. An IEL fraction prevented the proliferation of LN‐T stimulated with antigen and X‐irradiated spleen cells, or with anti‐CD3 monoclonal antibodies (mAb). Concanavalin A‐activated LN‐T were less sensitive. Such an inhibitory activity was recovered from a CD8‐depleted population by panning of bulk IEL using anti‐CD8α mAb. This population of BALB/c IEL showed less granzyme A activity, and its surface markers were positive for CD8 (∼4%), CD3 (80–90%), CD4 (2–6%), αβTcR (45–70%), and γδTcR (4–9%). Asialo‐GM1 and Thy1.2 were variably expressed, but interleukin‐2 (IL‐2) receptor‐α and FcγR were not. By contrast, no cytotoxicity against YAC‐1 was detected in a CD8‐depleted IEL population by a 6‐h 51Cr‐release assay. Although IEL from severe‐combined immunodeficient mice lacking CD4, CD8 and TcR, but expressing IL‐2 receptor, showed cytotoxicity against YAC‐1, their inhibitory activity against LN‐T was almost the same as that by IEL from BALB/c mice. When LN‐T blasts (>75% CD4+) activated with anti‐CD3 were treated with CD8‐depleted IEL, intact cellular DNA of the T blasts disappeared within 1 h with increased amounts of small‐sized DNA. These results suggest that CD8− IEL directly and nonspecifically kill lymph node CD4+ T blasts and possibly down‐regulate TcR‐mediated proliferation of peripheral T cells in the gut epithelium.
A third interferon‐γ‐induced subunit exchange in the 20S proteasome
Authors: Groettrup Marcus , Kraft Regine , Kostka Susanne , Standera Sybille , Stohwasser Ralf , Kloetzel Peter‐M. 
Published: March 2007

AbstractThe 20S proteasome is a protease complex of functional importance for antigen processing. Two of the 14 proteasome subunits, δ and MB1, can be replaced by the major histocompatibility complex (MHC)‐encoded and interferon‐γ (IFN–γ)‐inducible subunits LMP2 and LMP7, respectively. LMP2 and LMP7 alter the cleavage site specificity of the 20S proteasome and are required for the efficient generation of T cell epitopes from a number of viral proteins and for optimal MHC class I cell surface expression. We compared the 20S proteasome subunit pattern from IFN‐γ‐induced and non‐induced mouse fibroblasts on two‐dimensional gels and identified a third subunit exchange by microsequencing: the non‐MHC‐encoded subunit MECL‐1 is induced by IFN‐γ and replaces a so‐far barely characterized β subunit designated ‘MC14’. In analogy to LMP2 and LMP7, MECL‐1 may be functional in MHC class I‐restricted antigen presentation.
A novel “chimeric” antibody class in cartilaginous fish: IgM may not be the primordial immunoglobulin
Authors: Greenberg Andrew S. , Hughes Austin L. , Guo Jian , Avila David , McKinney E. Churchill , Flajnik Martin F. 
Published: March 2007

AbstractUsing a degenerate oligonucleotide primer specific for immunoglobulin (Ig) constant type 1 (C‐1 set) domain genes, products were amplified by the reverse transcriptase‐polymerase chain reaction from nurse shark spleen cDNA. The deduced protein sequence of one of these clones reveals a novel Ig class in cartilaginous fish. A complete mRNA could encode a mature protein bearing an amino‐terminal variable (V) domain, followed by six C‐1 set domains, and ending in a carboxy‐terminal tail typical of secreted IgM, IgA, and the new antigen receptor (NAR). The two amino‐terminal C domains are orthologous to IgX (or IgR), an Ig heavy (H) chain class in the skate, and the last four domains are homologous to the carboxy‐terminal four domains of NAR. We designate this “chimeric” Ig class IgNARC for Ig new antigen receptor from cartilaginous fish. Like NAR, but unlike shark IgM, IgNARC is encoded by very few V and C genes which apparently are not closely linked. The number of bands that hybridize with exon‐specific probes varies with genomic DNA from individual sharks, suggestive of different numbers of IgNARC genes in different animals. A protein of approximately 95 kDa, which is likely to be the IgNARC H chain, is immunoprecipitated with both light chain‐specific monoclonal antibodies and with antisera generated to a peptide comprising the IgNARC carboxy‐terminal tail. We conclude that the arsenal of secreted antigen receptors in cartilaginous fish is greater than previously believed. In addition, our data cast doubt on the dogma that IgM is the primordial Ig isotype.
Polyclonal expansion of adoptively transferred CD4+ αβ T cells in the colonic lamina propria of scid mice with colitis
Authors: Rudolphi Angelika , Bonhagen Kerstin , Reimann Jörg 
Published: March 2007

AbstractThe adoptive transfer of low numbers of peripheral, non‐fractionated CD4+ αβ T cells into histocompatible, severely immunodeficient (scid) hosts induces a colitis. This disease developed in C.B‐17 scid/scid hosts after the injection of 105CD4+ T cells purified from different peripheral lymphoid organs of immunocompetent C.B‐17 +/+ or BALB/cdm2 donor mice. Irrespective of their tissue origin, transferred CD4+ T cells selectively repopulated the scid host with gut‐seeking CD4+ T cells. A chronic inflammatory bowel disease (IBD) developed as polyclonal populations of mucosa‐seeking memory/effector CD4+ T cells accumulated in the gut lamina propria and epithelial layer of the adoptive host. The manifestation of colitis in the scid host correlated with the in situ polyclonal activation and expansion of adoptively transferred CD4+ T cells in the colonic lamina propria. Attempts were unsuccessful to select in vivo an oligoclonal CD4+ T cell population with an enhanced IBD‐inducing potential by repeatedly reinjecting 105 donor‐type CD4+ T cells from the colonic lamina propria of transplanted scid mice with an early and severe IBD into new scid hosts. The data indicate that the preferential repopulation of gut‐associated lymphoid tissues with immunocompetent CD4+ T cells, and their polyclonal activation and in situ expansion in the lamina propria of the histocompatible, immunodeficient host are critical events in the pathogenesis of an IBD in this model.
The role of oxygen in thymocyte apoptosis
Authors: McLaughlin Kelly A. , Osborne Barbara A. , Goldsby Richard A. 
Published: March 2007

AbstractSignals generated by T cell receptor (TCR) cross‐linking (or phorbol 12‐myristate‐13‐acetate + Ca2+ ionophore), glucocorticoids or ionizing radiation all stimulate apoptotic cell death in thymocytes by signals that are initially distinct from each other. However, when these stimuli were administered to thymocyte cultures that were maintained under an atmosphere containing less than 20 ppm oxygen as opposed to one that contained 18.5 % molecular oxygen, cell death was inhibited or abrogated, suggesting that the induction of death by all three different stimuli depend on the presence of molecular oxygen. Studies of the effects of the cysteine analog N‐acetyl cysteine (NAC) with normal thymocytes demonstrated that this antioxidant inhibited the induction of death by each of the different stimuli in a manner that paralleled anaerobiosis. Furthermore, studies with thymocytes demonstrated that the induction of nur77, a gene shown to be involved in thymocyte apoptosis signaled through the TCR or its surrogates, is not inhibited by NAC or dependent upon molecular oxygen. The possible implications for negative selection of NAC‐mediated inhibition of TCR‐signaled thymocyte cell death was examined in thymic organ culture. Treatment of these cultures with NAC provided significant protection against staphylococcal enterotoxin B‐mediated deletion of Vβ8‐expressing thymocytes.
Differential modulation of B7‐1 and B7‐2 isoform expression on human monocytes by cytokines which influence the development of T helper cell phenotype
Authors: Creery W. David , Diaz‐Mitoma Francisco , Filion Lionel , Kumar Ashok 
Published: March 2007

AbstractThe co‐stimulatory molecules B7‐1/B7‐2 expressed on the surface of antigen‐presenting cells have been suggested to influence the development of T helper 1 (Th1)‐versus Th2‐immune responses. These studies were conducted to elucidate the effect of immunoregulatory cytokines which influence the development of Th1/Th2 immune responses on the expression of the B7 isoforms B7‐1 and B7‐2 on resting and activated human monocytes and B cells. Interleukin (IL)‐4 and IL‐10, which induce the development of Th2 immune responses, down‐regulated B7‐2 and moderately up‐regulated B7‐1 expression on resting CD14+ monocytes in peripheral blood mononuclear cells. Interferon‐γ (IFN‐γ), which induces the development of Th1 immune responses, enhanced the expression of both B7‐1 and B7‐2 isoforms. Tumor necrosis factor (TNF)‐α, which elicits both Th1‐ and Th2 characteristics depending on experimental conditions, down‐regulated B7‐2 but did not alter B7‐1 expression. The effect of TNF‐ä and B7‐2 expression is not mediated through endogenously produced IL‐10, as addition of anti‐IL10 antibodies did not restore B7‐2 expression. None of the other cytokines tested, including IL‐1α, IL‐1β, IL‐2, IL‐5, IL‐6, IL‐12, granulocyte/macrophage colony‐stimulating factor (GM‐CSF), and transforming growth factor (TGF)‐α, modulated the expression of B7 isoforms on resting monocytes. Lipoolysaccharide stimulation of monocytes down‐regulated B7‐2 and up‐regulated B7‐1 expression in a manner similar to IL‐10. The expression of B7‐1 and B7‐2 on purified B cells were not altered by any of the cytokines tested, including IL‐1α, IL‐1β, IL‐2, IL‐4, IL‐5, IL‐6, IL‐10, IL‐12, IFN‐γ, TNF‐α, TGF‐α and GM‐CSF. Taken together, our results suggest that the cytokines which induce Th1/Th2 immune responses exert differential effects on B7 isoform expression on resting monocytes but have no effect on resting or activated B cells.
HLA‐associated inverse correlation between T cell and antibody responsiveness to islet autoantigen in recent‐onset insulin‐dependent diabetes mellitus
Authors: Roep Bart O. , Duinkerken Gaby , Schreuder Geziena M. T. , Kolb Hubert , de Vries René R. P. , Martin Stephan 
Published: March 2007

AbstractInsulin‐dependent diabetes mellitus (IDDM) is a T cell‐dependent immune‐mediated disease. Recently, a novel islet cell antigen (ICA69) recognized by autoantibodies was described. We tested T cell responsiveness to ICA69 in peripheral blood of patients with recent onset IDDM (n = 46), patients with long‐standing IDDM (n = 44), non‐diabetic age‐matched, islet cell autoantibody‐ and glutamic acid decarboxylase (GAD)65 antibody‐negative first‐degree relatives of IDDM patients (n = 15) and rheumatoid arthritis patients (n = 22). T cell responsiveness was significantly higher in recent onset IDDM patients, compared to IDDM patients post‐disease onset, non‐diabetic first degree relatives and rheumatoid arthritis patients (p < 0.001). In responding IDDM patients a significant inverse correlation between T cell and autoantibody responsiveness to ICA69 was observed (p < 0.0005). Immunogenetic evaluation revealed an association of HLA‐DR3 with T cell responsiveness to ICA69 (p < 0.02) and absence of ICA69‐reactive autoantibodies (p < 0.04). The increased T cell reactivity to ICA69 in the absence of antibody reactivity at onset of IDMM is associated with an HLA class II immune response gene, and therefore suggestive of a genetically controlled selective activation of T helper subsets to a specific autoantigen in humans.
Dispensability of Jak1 tyrosine kinase for interleukin‐2‐induced cell growth signaling in a human T cell line
Authors: Higuchi Masaya , Asao Hironobu , Tanaka Nobuyuki , Oda Katsuhiko , Takeshita Toshikazu , Nakamura Masataka , Van Snick Jacques , Sugamura Kazuo 
Published: March 2007

AbstractThe tyrosine kinases Jak1 and Jak3 are known to be associated with the β and γ chains of interleukin‐2 receptor (IL‐2R). They are activated by stimulation with IL‐2, IL‐4, IL‐7, IL‐9, or IL‐15, receptors of which share the γ chain of the IL‐2R. We have obtained direct evidence of Jak1 association with the α chains of receptors for IL‐4, IL‐7 and IL‐9 and with the β chain of IL‐2R, which is also common to the IL‐15R. Furthermore, we have prepared mutant IL‐2R β chains with a mutation in the box 1 region, which is conserved among the IL‐2R β chain and the α chains of the other cytokine receptors sharing the IL‐2R γ chain. Using MOLT‐4 transfectants with the mutant β chains, we found that two conserved proline residues within the box 1 region are essentially involved in association with Jak1. The MOLT‐4 transfectants with the mutant β chains lacking Jak1 association showed IL‐2 responsiveness, in terms of activation of Jak3 and Stat5 and induction of cell growth, indicating that Jak1 is dispensable for IL‐2‐mediated cell growth signaling and that Jak1 activation is not required for activation of Jak3 and Stat5 in the MOLT‐4 transfectants.
On the interaction between agalactosyl IgG and Fcγ receptors
Authors: Groenink Jasper , Spijker Jeroen , van den Herik‐Oudijk Ingrid E. , Boeije Leonie , Rook Graham , Aarden Lucien , Smeenk Ruud , van de Winkel Jan G. J. , van den Broek Maries F. 
Published: March 2007

AbstractOne of the serum abnormalities observed in autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) is the occurrence of IgG that lacks the terminal galactose on asparagine‐linked biantennary complex type oligosaccharides [Gal(0)‐IgG] located in the CH2 domain. Additionally, IgG without glycosylation is known to be defective in several effector functions due to a reduced ability to bind to its specific receptors (FcγR). It has thus been speculated that, by analogy with unglycosylated IgG, Gal(0)‐IgG may also be functionally impaired or exert altered effector mechanisms. If this were true, Gal(0)‐IgG could contribute to the phenotype of above‐mentioned autoimmune diseases, like impaired immune complex clearance and defective down‐regulation of activated B cells. Here, we show by three different methods that the interaction of Gal(0)‐IgG and normally glycosylated IgG with the low‐affinity FcγRII (CD32) is indistinguishable with respect both to binding and receptor‐mediated signalling. These data argue against a prominent role for FcγR‐dependent Gal(0)‐IgG interactions in the etiology or pathogenesis of autoimmune diseases.
Semi‐allogeneic (F1) versus fully allogeneic blood transfusions: differences in their ability to induce specific immunological unresponsiveness
Authors: Roelen Dave L. , Dover Emma L. , Niimi Masanori , Young Neil T. , Morris Peter J. , Wood Kathryn J. 
Published: March 2007

AbstractThe beneficial effect on graft survival achieved by pretransplant blood transfusions is well established. However, the type of major histocompatibility complex (MHC) mismatch between transfusion donor and recipient seems to play a role in determining the outcome. The hypothesis that this sharing of MHC antigens is correlated with the level of sensitization or tolerization was studied in mice by pretreatment with semi‐allogeneic (F1) or with fully allogeneic whole blood transfusions. Limiting dilution analysis (LDA) in vitro for donor‐specific T helper (Thp) and cytotoxic T lymphocyte precursors (CTLp) performed on splenocytes isolated from transfused recipients 2 or 4 weeks after transfusion showed that the duration and magnitude of the response was reduced after a semi‐allogeneic compared to a fully allogeneic transfusion. After a semi‐allogeneic transfusion, both Thp and CTLp frequencies had returned to naive levels 4 weeks after transfusion, whereas after infusion of fully allogeneic blood, they remained elevated after 4 weeks. When a fully allogeneic heart was transplanted 2 or 4 weeks after transfusion, a small but significant improvement in graft prolongation (2 weeks, not significant, 4 weeks: p < 0.01) was observed following pretreatment with a semi‐allogeneic transfusion (2 weeks: median survival time (MST) 30 days, 4 weeks: MST 29 days) compared to that obtained after fully allogeneic transfusion (2 weeks: MST 23 days, 4 weeks: MST 12 days). The semi‐allogeneic transfusions were correlated with a statistically significant prolonged (7 days) persistence of donor‐derived MHC class II+ cells in the recipient and with reduced levels of anti‐donor MHC class I‐specific antibody formation compared to these responses after transfusion with fully allogeneic cells. These results demonstrate that pretreatment with a semi‐allogeneic blood transfusion is more tolerizing and less sensitizing than pretreatment with a fully allogeneic blood transfusion. These findings may be explained by the sharing of MHC antigens between recipient and transfusion donor.
Neonatal and early life immune responses to various forms of vaccine antigens qualitatively differ from adult responses: predominance of a Th2‐biased pattern which persists after adult boosting
Authors: Barrios Christy , Brawand Pierre , Berney Monika , Brandt Christian , Lambert Paul‐Henri , Siegrist Claire‐Anne 
Published: March 2007

AbstractInduction of neonatal immune responses to vaccine antigens is believed to be of limited efficacy because of immune immaturity and particular susceptibility to tolerogenic signals during this period of life. To characterize particular features of neonatal immune responses to vaccine antigens, we assessed the capacity of BALB/c mice at different stages of immunological maturation to respond to a selection of vaccine antigens and presentation systems. Significant B and T cell responses to vaccine antigens (tetanus and measles virus peptides, tetanus toxoid, live viral attenuated measles virus, canarypox recombinant measles vector or bacillus Calmette‐Guérin) were obtained as early as the first week of life. However, these neonatal responses differed qualitatively from adult responses by a decreased IgG2a/IgG1 ratio of vaccine‐specific antibodies, the secretion of significantly higher interleukin‐5 and lower interferon‐γ levels by vaccine‐specific T cells and an impaired induction of cytotoxic T cell precursors. This pattern of biased Th2 versus Th1 responses induced upon early exposure to vaccines was not reversed by decreasing the doses of vaccine antigens. It did not disappear with aging and was still reflected in adult responses to booster immunization with the corresponding antigen. Thus, neonatal immunization can induce significant vaccine specific responses with a predominance of a Th2 pattern which can persist in boosted adult mice.
Human lymphocytes shed a soluble form of CD21 (the C3dg/Epstein‐Barr virus receptor, CR2) that binds iC3b and CD23
Authors: Frémeaux‐Bacchi Véronique , Bernard Isabelle , Maillet Françoise , Mani Jean‐Claude , Fontaine Marc , Bonnefoy Jean‐Yves , Kazatchkine Michel D. , Fischer Elizabeth 
Published: March 2007

AbstractWe report on a soluble (s) form of CD21 (the C3dg/Epstein‐Barr virus receptor, CR2) that is spontaneously released by B and T lymphocytes. Immunoprecipitation with anti‐CD21 mAb of culture supernatants of surface and biosynthetically labeled B and T cell lines revealed a single band with an apparent molecular mass of 135 kDa. The molecule exhibited a molecular mass 10 kDa lower than that of membrane CD21. The release of soluble CD21 (sCD21) was time dependent and correlated with a parallel decrease in the expression of the membrane‐associated molecule. The protein was also found in culture supernatants of tonsillar B cells and normal human thymocytes. Epitopic analysis using combinations of anti‐CD21 monoclonal antibodies (mAb) indicated that sCD21 and membrane CD21 were similarly recognized by mAb directed against short concensus repeats (SCR) 1–2, SCR 4–5 and SCR 9–11. Affinity‐purified sCD21 was capable of binding to purified human iC3b and to human recombinant CD23, as assessed by enzyme‐linked immunosorbent assay and by using the BIAcoreTM technology. In addition, normal human serum was found to contain a soluble form of CD21 that exhibited a similar molecular mass to that of the molecule shed by B and T cells in culture. The serum form of CD21 was recognized by all anti‐CD21 mAb that we tested and showed a high reactivity with mAb directed against SCR 1–2. Our observations suggest that B and T cells shed the extracellular portion of CD21 and release a soluble molecule that retains the ligand‐binding properties of CD21, thus having a potential role in immunoregulation.
An IgG‐transporting Fc receptor expressed in the syncytiotrophoblast of human placenta
Authors: Simister Neil E. , Story Craig M. , Chen Hua‐Liu , Hunt Joan S. 
Published: March 2007

AbstractDuring normal human pregnancy, maternal IgG crosses the placenta and provides passive immunity for the fetus. In so doing, IgG passes through two cellular barriers: the syncytiotrophoblast and the fetal capillary endothelium. The Fc region of IgG is required for its transport across the placenta, but the Fc receptors responsible have not been identified definitively. We recently reported the isolation from a placental cDNA library of clones encoding the α chain of a human homologue of the major histocompatibility complex class I‐related Fc receptor, the neonatal Fc receptor (FcRn). In mice, FcRn is essential for the transport of maternal IgG to the fetus and the neonate. We report here the localization of human FcRn mRNA within the placenta by in situ hybridization, and of human FcRn protein by immunohistochemistry. Both methods show that human FcRn is expressed in syncytiotrophoblast, and is, thus, appropriately located to transport maternal IgG across the first barrier. We confirm previous findings that specific binding of IgG to placental membranes is greater at pH 6.0 than pH 7.5. This corresponds with the pH dependence of IgG binding to FcRn and is consistent with the presence of FcRn in syncytiotrophoblast. We propose a transport model in which maternal IgG binds FcRn at low pH in endosomes within the syncytiotrophoblast. FcRn is not expressed in fetal capillary endothelia, and the mechanism of IgG transport across the second barrier remains unknown.
CD28/CTLA4‐B7 interaction is dispensable for T cell stimulation by mouse mammary tumor virus superantigen but not for B cell differentiation and virus dissemination
Authors: Champagne Eric , Scarpellino Leonardo , Lane Peter , Acha‐Orbea Hans 
Published: March 2007

AbstractB cells are the primary targets of infection for mouse mammary tumor virus (MMTV). However, for productive retroviral infection, T cell stimulation through the virally‐encoded superantigen (SAG) is necessary. It activates B cells and leads to cell division and differentiation. To characterize the role of B cell differentiation for the MMTV life cycle, we studied the course of infection in transgenic mice deficient for CD28/CTLA4‐B7 interactions (mCTLA4‐Hγ1 transgenic mice). B cell infection occurred in CTLA4‐Hγ1 transgenic mice as integrated proviral DNA could be detected in draining lymph node cells early after infection by polymerase chain reaction analysis. In mice expressing I‐E, B cells were able to present the viral SAG efficiently to Vβ6+ T cells. These cells expanded specifically and were triggered to express the activation marker CD69. Further stages of progression of infection appeared to be defective. Kinetics experiments indicated that T and B cell stimulation stopped more rapidly than in control mice. B cells acquired an activated CD69+ phenotype, were induced to produce IgM but only partially switched to IgG secretion. Finally, the dissemination of infected cells to other lymph nodes and spleen was reduced and the peripheral deletion of Vβ6+ T cells was minimal. In contrast, in mice lacking I‐E, T cell stimulation was also impaired and B cell activation undetectable. These data implicate B7‐dependent cellular interactions for superantigenic T cell stimulation by low‐affinity TCR ligands and suggest a role of B cell differentiation in viral dissemination and peripheral T cell deletion.