bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell surface expression of surrogate light chain (ΨL) in the absence of μ on human pro‐B cell lines and normal pro‐B cells
Authors: Meffre Eric , Fougereau Michel , Argenson Jean‐Noël , Aubaniac Jean‐Manuel , Schiff Claudine 
Published: March 2007

AbstractSurrogate light chains (ΨL) encoded by λ‐like (λ5) and VpreB genes play a critical role in controlling the early steps of B cell differentiation. We prepared new anti‐VpreB monoclonal antibodies (mAb) (3C7/6F6) which preferentially recognize the VpreB epitope at the cell surface of human cell lines that do not express the μ chain. These mAb provide the first characterization of human pro‐B cell lines expressing surface ΨL. We demonstrate that surface ΨL expression is considerably enhanced upon interleukin‐7 stimulation and that the ΨL complex is formed independently of the Igα/Igβ heterodimer. Finally, using these antibodies, we confirm the existence of a normal pro‐B cell population in human adult bone marrow. These cells are CD34+ CD38+ ΨL+, do or do not express CD19, CD10, or both epitopes, and may represent the earliest cell population committed to B cell differentiation.
The fate of adoptively transferred antigen‐specific T cells in vivo
Authors: Zhang Li 
Published: March 2007

AbstractIn this study, anti‐major histocompatibility complex class I Ld T cell receptor (TCR)‐transgenic cells were adoptively transferred into severe‐combined immunodeficient (Scid) mice which express the Ld Ag on all nucleated cells, and the fate of transferred antigen‐specific T cells (ASTC) was followed in vivo. It was found that, after encountering antigen (Ag) in vivo, the number of ASTC increased 10–15‐fold followed by a decline in number to a value that was still above the starting value. The expansion of ASTC could be abrogated by blocking CD28 on the T cells prior to Ag stimulation. Using the technique which simultaneously stains ASTC surface markers and apoptotic cells, we have not only demonstrated directly that the ASTC that disappeared from the periphery died by activation‐induced apoptosis but also studied their kinetics in vivo. The remaining ASTC moderately down‐regulated both TCR and CD8 on their cell surface and were fully unresponsive when cultured with Ld+ cells even in the presence of exogenous interleukin (IL)‐2 and IL‐4. However, they were still susceptible to apoptosis when transfereed into a secondary host that provided a new source of Ag and antigen‐presenting cells. These studies indicate that peripheral T cell tolerance can be induced by multiple mechanisms in which activation‐induced ASTC apoptosis plays an important role.
Induction of sensitivity to activation‐induced death in primary CD4+ cells: A role for interleukin‐2 in the negative regulation of responses by mature CD4+ T cells
Authors: Wang Ruduan , Rogers Amy M. , Rush Brian J. , Russell John H. 
Published: March 2007

AbstractWe examine the requirements for converting naive, mature CD4+ cells from an activation‐induced death (AID)‐resistant to a ‐sensitive phenotype. Priming for sensitivity to AID can be divided into two steps. The first is a mitogen/CD3‐dependent, cyclosporin‐sensitive signal and the second a cytokine‐dependent, cyclosporin‐insensitive one. Under these conditions, interleukin (IL)‐2, but not IL‐4, IL‐7 or IL‐15, the receptors of which share a common receptor γ chain, is capable of providing the cytokine signal for inducing sensitivity to AID. Increased expression of the low‐affinity IL‐2Rα chain (CD25) is associated with acquisition of AID sensitivity and antibodies to CD25 block acquisition of AID sensitivity in the presence of IL‐2. As with T cell hybridomas, AID is dependent on both CD95 and CD95 ligand (CD95L) expression, but unlike hybridomas, the sensitive and resistant phenotypes of primary CD4+ cells cannot be distinguished by levels of CD95 expression, functional CD95L nor the fraction of cells in cycle. The results suggest that the unique function of IL‐2 is to regulate proteins, either not important or constitutively regulated in T cell hybridomas, that are essential for cell‐autonomous suicide of activated CD4+ cells. These experiments provide a mechanism for the recent observations of chronic lymphoproliferation and autoimmune disease in mice with null mutations in IL‐2 or CD25.
Human B7‐1 is more efficient than B7‐2 in providing co‐stimulation for alloantigen‐specific T cells
Authors: van Dijk Astrid M. C. , Otten Henny G. , Vercauteren Suzanne M. , Kessler Floortje L. , de Boer Mark , Yerdonck Leo F. , de Gast Gijsbert C. 
Published: March 2007

AbstractBesides a signal via the T cell receptor/CD3 complex, an additional co‐stimulatory signal is required for optimal T cell activation. This signal can be delivered by interaction of either B7‐1 or B7‐2 expressed by antigen‐presenting cells with CD28 on the T cells. Comparison of the function of B7‐1 and B7‐2 in different experimental animal systems generated conflicting data on the roles for the co‐stimulatory molecules. We therefore investigated whether there are differences between B7‐1 and B7‐2‐mediated co‐stimulation in an alloantigen‐specific primary T cell response induced by B7‐transfected human cell lines of epithelial origin. Both transfected keratinocyte cell lines efficiently induce T cell proliferation and the ratios of stimulator versus responder cells are similar. The kinetics of proliferation and interleukin (IL)‐2, IL‐4 and interferon‐γ production are also comparable between both transfectant lines. However, despite equal B7 expression levels, it is consistently found that the magnitude of the B7‐1‐induced T cell proliferation was higher than that of B7‐2. Comparison of precursor frequencies of helper T lymphocytes responsive with either B7‐1 or B7‐2 revealed that the frequency of B7‐1‐responsive T cells was higher than that of B7‐2, and that the frequency of cells activated by a combination of B7‐1 and B7‐2 did not differ significantly from that of B7‐1 alone. We therefore conclude that the B7‐2‐responsive T cells are part of the B7‐1‐responsive population, and that B7‐1 on keratinocytes is more efficient in providing co‐stimulation for alloantigen‐specific T cells.
Prevention and amelioration of collagen‐induced arthritis by blockade of the CD28 co‐stimulatory pathway: requirement for both B7‐1 and B7‐2
Authors: Webb Louise M. C. , Walmsley Marita J. , Feldmann Marc 
Published: March 2007

AbstractCollagen type II‐induced arthritis (CIA) is an experimental model of arthritis that has been successfully used to dissect the pathogenesis of human rheumatoid arthritis and to identify potential therapeutic targets. We have used this model to evaluate the role of T cell co‐stimulation in both disease development and progression. T cell co‐stimulation is provided by ligation of CD28 with either B7‐1 or B7‐2 present on antigen‐presenting cells and can be prevented by a soluble form of CTLA‐4 (CTLA‐4Ig) which binds with high affinity to both B7‐1 and B7‐2. We found that administration of CTLA‐4Ig at the time of immunization prevented the development of CIA and was associated with lack of lymphocyte expansion within the draining lymph node and failure to produce anti‐collagen IgG1 or IgG2a antibodies. To determine which CD28 ligand plays a more dominant role in CIA, we treated mice with monoclonal antibodies (mAb) against either B7‐1 or B7‐2. Neither anti‐B7‐1 nor anti‐B7‐2 had any effect on the course of CIA when given alone, but resulted in reduced incidence and clinical scores when given together. Interestingly, when treatment was delayed until after the onset of clinical disease, both CTLA‐4Ig or anti‐B7‐1 plus anti‐B7‐2 mAb still ameliorated disease. Effective treatment was associated with a reduction in interferon‐γ production by lymph node cells following stimulation in vitro, suggesting that Th1 responses were diminished. This study points to a critical role of CD28 co‐stimulation in the development and perpetuation of CIA in DBA/1 mice. Interestingly, it demonstrates an active role for T cells in the later stages of this disease and implicates both B7‐1 and B7‐2‐mediated co‐stimulation in the pathogenesis of CIA.
A novel nucleotide‐containing antigen for human blood γδ T lymphocytes
Authors: Poquet Yannick , Constant Patricia , Halary Franck , Peyrat Marie‐Alix , Gilleron Martine , Davodeau François , Bonneville Marc , Fournié Jean‐Jacques 
Published: March 2007

AbstractThe stimulation of human γδ T cells by mycobacteria occurs through recognition of four distinct nonpeptide phosphorylated antigens termed TUBag1–4. Among these latter, TUBag4 has already been biochemically characterized as a γ‐X derivative of 5′‐deoxythymidine triphosphate (Constant, P., Davodeau, F., Peyrat, M. A., Poquet, Y., Puzo, G., Bonneville, M. and Fournié, J.‐J., Science 1994. 264: 267). However, despite chemical synthesis of weakly stimulatory nucleotide‐containing analogs, these mycobacterial compounds remained the sole nucleotide‐containing antigens actually isolated from natural sources. Here, we present the complete isolation of the TUBag3 antigen from Mycobacterium fortuitum and demonstrate that this nonpeptide molecule contains a 5′‐UTP nucleotide moiety. On selected Vγ9/Vδ2 clones, T cell responses can be triggered with nanomolar concentrations of TUBag3. Like crude mycobacterial extracts, this purified nucleotide conjugate elicits a strong polyclonal response of γδ PBL from healthy donors. Furthermore, we present evidence that this compound is distinct from the recently synthesized γ‐isopentenyl 5′‐UTP, a nucleotide conjugate of isopentenyl pyrophosphate that was found to be stimulatory for human γδ T cells (Tanaka, Y., Morita, C. T., Tanaka, Y., Nieves, E., Brenner, M. B. and Bloom, B. R., Nature 1995. 375: 155). Since it appears that both mycobacterial nucleotide antigens are molecules structurally related to peculiar precursors of nucleic acid synthesis, we propose that TUBag‐reactive T cells might be specifically devoted to surveillance of proliferating cells.
Raf regulates positive selection
Authors: O'Shea Clodagh C. , Crompton Tessa , Rosewell Ian R. , Hayday Adrian C. , Owen Michael J. 
Published: March 2007

AbstractT cell development is regulated by extracellular signals that mediate cellular proliferation and differentiation via specific signal transduction pathways. To determine the importance of the mitogen‐activated protein kinase (MAP kinase) pathway in thymocyte development, we analyzed transgenic mice expressing dominant negative Raf (DN Raf) and a constitutively active v‐Raf under the control of the p56lck proximal promoter. DN Raf had a profound effect on T cell receptor (TCR)‐mediated signaling events as assessed by the inhibition of mitogen‐induced proliferation of thymocytes in vitro. Overall thymocyte numbers were decreased by at most twofold from nontransgenic littermates. Positive selection was inhibited in DN Raf transgenic mice, as evidenced by both reduced numbers of mature thymocytes and a decrease in CD8+ thymocytes in female mice doubly transgenic for DN‐Raf and a class I‐restricted H‐Y TCR. In contrast, the differentiation of double‐positive thymocytes to single‐positive thymocytes was enhanced in H‐YTCR transgenic mice expressing constitutively active Raf (v‐Raf). Thus, Raf regulates positive selection in the thymus.
Identification and cellular distribution of the rat interleukin‐2 receptor β chain: induction of the IL‐2Rα−β+ phenotype by major histocompatibility complex class I recognition during T cell development in vivo and by T cell receptor stimulation of CD4+8+ immature thymocytes in vitro
Authors: Park Jung‐Hyun , Hanke Thomas , Hünig Thomas 
Published: March 2007

AbstractA mouse monoclonal antibody (mAb) to the rat interleukin‐2 receptor β (IL‐2Rβ) chain was generated using IL‐2Rβ cDNA‐transfected mouse L929 cells for immunization and differential screening. This antibody, called L316, detects a cell surface protein with an apparent molecular mass of about 80 kDa. In peripheral lymphoid organs of young adult rats, IL‐2Rβ expression is restricted to T and natural killer (NK) cells, and less than 10% of IL‐2Rβ+ cells co‐express the IL‐2Rα chain. IL‐2Rβ was detected on all NKRP‐1hi (NK−) and NKRP‐1lo cells (T‐lineage cells of unknown function), most peripheral γδ T cells and on 30–40% of CD8 and 10% of CD4 αβ T cells. In the adult rat thymus, mAb L316 detects a small subset (about 1%) of predominantly IL‐2Rα− cells which express cell surface markers characteristic of mature T lymphocytes and contain a high proportion of CD4−8− and CD4−8+ αβ T cell receptor (TCR)+ thymocytes. TCR‐V usage suggests that major histocompatibility complex (MHC) class I plays a more important role than MHC class II in the selection of these cells. On immature CD4+8+ rat thymocytes, IL‐2Rβ cell surface expression is readily induced by TCR stimulation in vitro, supporting the idea that in vivo, the IL‐2Rβ+ phenotype is the result of TCR engagement during thymic selection.
Th1/Th2 cytokine gene expression after mercuric chloride in susceptible and resistant rat strains
Authors: Gillespie Kathleen M. , Saoudi Abdelhadi , Kuhn Joëlle , Whittle Catheryne J. , Druet Philippe , Bellon Blanche , Mathieson Peter W. 
Published: March 2007

AbstractMercuric chloride (HgCl2) has contrasting effects on different rat strains: susceptible strains, e.g. Brown Norway (BN) develop polyclonal B cell activation, multiple autoantibodies and widespread tissue injury. Lewis (LEW) rats are resistant: no autoimmune response occurs after HgCl2; instead, there is immunosuppression. We have previously shown, by fully quantitative polymerase chain reaction (PCR), up‐regulation of interleukin‐4 (IL‐4) gene expression in HgCl2‐treated BN rats, implicating Th2 cells in the autoimmune syndrome. Involvement of the reciprocal Th1 subset, producing interferon‐γ (IFN‐γ), in resistance of LEW rats to HgCl2 has been suggested. We now report extensive analysis of Th1 and Th2 cytokine gene expression in spleen and lymph nodes of susceptible (BN) and resistant (LEW) rats after HgCl2. IL‐4 and IFN‐γ were analyzed by quantitative PCR, other cytokines were assessed using semiquantitative PCR: the relative merits of these two techniques are discussed. We show pronounced up‐regulation of IL‐4 and more modest up‐regulation of IFN‐γ in BN rats, but no up‐regulation of either in LEW rats. Baseline levels of IFN‐γ were higher in LEW rats. Semi‐quantitative PCR showed increased expression of IL‐2, IL‐6 and IL‐10 in BN; in LEW rats only IL‐10 was increased. There was no marked change in IL‐5, IL‐13 or transforming growth factor‐β (TGF‐β) in either strain. These data further support the key role of IL‐4 in HgCl2‐induced autoimmunity, and suggest that failure of up‐regulation of IL‐4, together with higher baseline IFN‐γ expression, accounts for resistance of LEW rats to HgCl2. However, neither IFN‐γ nor TGF‐β can be implicated in HgCl2‐induced immunosuppression in the LEW rat in vivo: our data suggest a role for IL‐10 in this phenomenon.
Phenotype, and migration properties of three major subsets of tissue homing T cells in sheep
Authors: Mackay Charles R. , Andrew David P. , Briskin Michael , Ringler Douglas J. , Butcher Eugene C. 
Published: March 2007

AbstractT cells show a bias in their migration pathways: some T cells preferentially migrate to peripheral lymph nodes (LN), some to mucosal tissues, and some to peripheral tissues such as skin. These recirculation pathways were examined in sheep by collecting lymph draining into and out of peripheral and intestinal LN, and using fluorescent dyes to trace the recirculation of the lymph cells. Monoclonal antibodies (mAb) to α4, β1, and β7 integrins, and L‐selectin, were used to define three major populations of recirculating T cells. Naive‐type T cells (L‐selectin+, α4β1lo β7lo) migrated preferentially through peripheral LN. Two memory populations could be defined: α4β1hi β7− and α4β7hiβ1lo. α4β1hi β7− T cells were present in lymph draining from the skin. T cells migrating preferentially through intestinal LN were α4β7hi β1lo. Consistent with this migration pattern, the endothelial receptor for α4β7, mucosal addressin cell adhesion molecule‐1 (MAdCAM‐1) was detected on high endothelial venules within intestinal LN and Peyer's patches, but only weakly on high endothelial venules within peripheral LN. Thus, there are at least three easily definable subsets of T cells, based on integrin expression, which show distinct migration preferences.
Comparison of rheumatoid factors of rheumatoid arthritis patients, of individuals with mycobacterial infections and of normal controls: evidence for maturation in the absence of an autoimmune response
Authors: Djavad Nargues , Bas Sylvette , Shi Xiaowen , Schwager Joseph , Jeannet Michel , Vischer Thomas , Roosnek Eddy 
Published: March 2007

AbstractWe analyzed the rheumatoid factors (RF) produced by Epstein‐Barr virus‐transformed monoclonal B cells established from four patients with rheumatoid arthritis (RA), three individuals with a history of Mycobacterium tuberculosis (TB) and four normal controls (NI). Fifty‐eight RF were analyzed for specific activity (international units‐RF/μg) for the Fc part of IgG and their interaction with tetanus toxoid (TT) and DNA (polyspecificity). Furthermore, we sequenced the V‐D‐J heavy chain region of 16 (9TB‐/7RA‐) RF. Significant differences were observed between the NI‐RF and the TB‐ and RA‐RF. While the RF repertoire of normal individuals comprised of low‐avidity RF of which the majority (15/17) were polyspecific, more than half of the TB‐ and RA‐RF were monoreactive. Furthermore, the monospecific TB‐ and RA‐RF were of significantly higher avidity than the NI‐RF (RA > TB ≫ NI). With respect to poly‐specificity, the RF in the three groups were comparable: the interaction with DNA, TT as well as with Fc was inhibited either by an increase of the ionic strength to 0.3–0.5 M NaCl or by addition of the polyanion dextran sulfate, indicating that the antibodies interacted with similar anionic epitopes shared by the three antigens. Analysis of the V‐D‐J heavy chain regions showed significant differences between the respective RF. The salt‐sensitive binding was highly correlated with the presence of arginine in the complementarity‐determining region 3 (CDR3). Furthermore, whereas the polyspecific RF consisted predominantly of germ‐line encoded antibodies, the genes of the monospecific RA/TB‐RF were somatically mutated (RA > TB). It is therefore likely that maturation of RF can be initiated by chronic infections and that monospecific, somatically mutated RF are not a unique characteristic of autoimmune diseases.
Localization of the site of the IgG molecule that regulates maternofetal transmission in mice
Authors: Medesan Corneliu , Radu Caius , Kim Jin‐Kyoo , Ghetie Victor , Ward E. Sally 
Published: March 2007

AbstractSite‐directed mutagenesis of a recombinant Fc hinge fragment has recently been used to localize the site of the mouse IgG1 (mIgG1) molecule that is involved in the intestinal transfer of recombinant Fc hinge fragments in neonatal mice. This site encompasses Ile‐253, His‐310, Gln‐311, His‐433 and Asn‐434, localized at the CH2‐CH3 domain interface and overlapping with the staphylococcal protein A‐binding and catabolic sites. In the present study, the effect of these mutations on the maternofetal transfer of Fc hinge fragments has been studied. Experiments to analyze transfer of radiolabeled Fc hinge fragments from the circulation of 15–18 day pregnant mice to fetuses in utero demonstrate that the mutations affect the maternofetal transmission in a way that correlates closely with the effects of the mutations on intestinal transfer and catabolism. The studies indicate that the neonatal Fc receptor, FcRn, is involved in transcytosis across both yolk sac and neonatal intestine in addition to the regulation of IgG catabolism.
Adult bone marrow contains precursors for CD5+ B cells
Authors: Huang Christene A. , Henry Cassis , Iacomini John , Imanishi‐Kari Thereza , Wortis Henry H. 
Published: March 2007

AbstractTo determine directly whether B cell precursors of adult origin are capable of generating CD5+ B cells, we reconstituted neonatal C3H.SCID mice with adult C57BL/6 bone marrow and analyzed splenic B cells 10 months later. Surface staining and flow cytometry revealed that the B cells were of donor origin and that 30% were CD5+. This confirms that in vivo generated CD5+ B cells can be adult derived. After anti‐IgM (but not lipopolysaccharide) stimulation in vitro, virtually all of the B cells from the bone marrow‐reconstituted mice expressed surface CD5. Sequence analysis of expressed VHDJH genes from the CD5+ B cells present after anti‐IgM stimulation revealed a high frequency of N nucleotide addition in CDR3 regions. The presence of N nucleotides indicates that these sequences were derived from CD5+ B cells of adult origin rather than from long‐lived fetal precursor B cells present in either the adult bone marrow at the time of transfer or adult spleen. These experiments demonstrate conclusively that adult bone marrow contains precursors for CD5+ B cells and that unlike fetal liver‐derived precursors these express terminal deoxynucleotidyl transferase.
Diversion of CD4+ T cell development from regulatory T helper to effector T helper cells alters the contact hypersensitivity response
Authors: Diiulio Nancy A. , Xu Hui , Fairchild Robert L. 
Published: March 2007

AbstractCutaneous sensitization to reactive haptens and subsequent challenge results in a T cell‐mediated response, contact hypersensitivity (CHS). Recent results from this laboratory have indicated that hapten sensitization induces two populations of reactive T cells: CD8+ T cells producing interferon (IFN)‐γ which mediate the response and CD4+ T cells producing interleukin (IL)‐4 and IL‐10 which negatively regulate the magnitude and duration of the response. Since CD4+ T cell development to either IFN‐γ‐ (Th1) or IL‐4/IL‐10‐ (Th2)‐producing cells is dependent upon the cytokine environment during antigen priming, we hypothesized that CD4+ T cell induction in a Th1‐promoting environment would not only alter the CD4+ T cell cytokine‐producing phenotype but also the course of the CHS response. Administration of the Th1‐promoting cytokine IL‐12 during hapten sensitization resulted in a CHS response of greater magnitude following challenge and extended the duration of the response. In hapten‐sensitized mice depleted of CD8+ T cells, treatment with IL‐12 induced effector CD4+ T cells. Histological examination of challenged ear tissue from these mice indicated minimal edema and an acute mononuclear cell infiltration more typical of classical delayed‐type hypersensitivity than CHS. Hapten‐primed CD4+ T cells from IL‐12 treated, sensitized mice produced IFN‐γ, but not IL‐4 in response to T cell receptor‐mediated stimulation. Use of neutralizing anti‐IFN‐γ antibody indicated that IL‐12 not only directly promoted Th1 development but also indirectly inhibited Th2 development through stimulation of IFN‐γ production at the time of hapten sensitization. Overall, these results demonstrate that diversion of CD4+ T cell development to Th1 effector cells rather than to Th2 cells alters the efferent nature of CHS and removes a primary regulatory mechanism of the immune response.