bluuebunny/crossref_metadata_2025_split huggingface dataset:
Normal clonal expansion but impaired Fasmediated cell death and anergy induction in interleukin‐2‐deficient mice
Authors: Kneitz Burkhard , Herrmann Thomas , Yonehara Shin , Schimpl Anneliese 
Published: March 2007

AbstractDespite a normal development of all major lymphoid subsets, with time, interleukin‐2 (IL‐2)‐deficient mice develop a fatal immunopathology. The disease phenotype is characterized by lymphoadenopathy, splenomegaly, T cell infiltration of various organs, overproduction of a number of cytokines and autoantibody formation. Phenotypically, CD4+ and CD8+ T cells exhibit features characteristic of antigenically experienced cells. The accumulation of cells with a memory phenotype together with the previous suggestion of an involvement of IL‐2 in the termination phase of immune responses prompted us to study the fate of superantigen‐reactive T cells in IL‐2‐deficient mice in comparison to their IL‐2‐producing littermates. We show that expansion in vivo of CD4+ and, to a lesser extent, CD8+ T cells reactive to the superantigens staphylococcal enterotoxin A and B (SEA and SEB) proceeds normally in the absence of IL‐2, but that fewer CD4+ cells are subsequently deleted. The residual superantigenreactive cells fail to become anergic as measured by proliferation in vitro in response to the same superantigen. T cell blasts generated in vitro from lymph node cells of IL‐2‐deficient mice by superantigen stimulation in the absence of exogenous IL‐2 also fail to become anergic. In contrast to cells from IL‐2‐producing littermates, they do not exhibit Fas‐induced apoptosis when cultured on anti‐Fas antibody‐coated plates, although Fas expression by IL‐2‐deficient cells is normal or even elevated compared to the IL‐2‐producing control cells. The data suggest that activation of T cells in the absence of IL‐2 fails to generate a signal which is necessary to activate the apoptotic pathway and thus leads to an accumulation of antigen‐experienced cells and the chronic inflammatory responses observed in IL‐2‐deficient mice.
T lymphocytes from normal human peritoneum are phenotypically different from their counterparts in peripheral blood and CD3− lymphocyte subsets contain mRNA for the recombination activating gene RAG‐1
Authors: Hartmann Johannes , Maaßen Volker , Rieber Peter , Fricke Harald 
Published: March 2007

AbstractThe surface antigens of peritoneal lymphocytes of healthy human individuals were studied. B lineage cells comprised 2.3% of the total peritoneal lymphocyte population. Although the majority of peritoneal cavity lymphocyte (PCL) T cells expressed αβ T cell receptor (TcR), up to 17% expressed γδ TcR. The majority of PCL exhibited markers of the thymus‐dependent lineage (CD2+ CD3+ Tcαβ+ CD4+ or CD8α+β+) and surface antigens associated with memory and activation (CD45RO+ CD11a+ CD18+ CD49d+ HLA‐DR). Up to 92% of both CD4+ and CD8+ T cells bore CDw60, thus characterizing the T cell subset containing helper activity for mitogen‐driven B cell differentiation. The majority of PCL T cells were CD8+ and, in addition, up to 60% of this population expressed the homodimeric CD8α+β−. Messenger RNA for the recombination activating gene RAG‐1 was examined in CD3− PCL depleted of CD19+ lineage cells. The PCL population which comprised cells containing RAG‐1 mRNA transcripts was CD19−, surface IgM−, cytoplasmic IgM− and CD2− CD3− CD4− CD8− CD56−. However, this population was CD7+ (approx. 75%), and contained both CD7−CD34+ (up to 3%) and CD7+ CD34+ (up to 3%) cells. These findings are compatible with the hypothesis that the adult human peritoneum provides a microenvironment capable of supporting a thymus‐indenpendent differentiation of T lymphocytes.
Epstein‐Barr virus/C3d receptor (CR2, CD21) activated by its extracellular ligands regulates pp105 phosphorylation through two distinct pathways
Authors: Bouillie Sylvie , Barel Monique , Drane Pascal , Cassinat Bruno , Balbo Michelle , Holers V. Michael , Frade Raymond 
Published: March 2007

AbstractWe previously demonstrated that human C3d or pep16, a 16‐amino acid synthetic peptide derived from human C3d, induced in vivo and in vitro tyrosine phosphorylation of pp105, an intracellular component found only in human cells that express CR2 at their surface. To determine the contribution of CR2 molecules to this enzymatic regulation, we first analyzed whether activation of CR2 by other extracellular CR2 ligands could trigger such regulation in cell extracts. Subsequently, we used cell extracts of either CR2‐positive cells depleted in CR2 molecules by absorption with anti‐CR2 antibodies or CR2‐negative cells transfected with CR2 cDNA. We demonstrate here that pp105 phosphorylation was induced when CR2 was activated by C3d and pep16 as well as by gp350, the Epstein‐Barr virus capsid protein or OKB7, an anti‐CR2 monoclonal antibody (mAb). HB5, another anti‐CR2 mAb, which did not activate B lymphocytes through CR2, did not induce pp105 phosphorylation. Thus, C3d, pep16, gp350, and OKB7 presented similar properties in activating CR2 to trigger pp105 phosphorylation and in regulating B lymphocyte proliferation, while HB‐5 had no effect on either assays. Furthermore, our data demonstrate that the presence of CR2 activated by its extracellular ligands regulates pp105 phosphorylation through two distinct pathways: one which also requires the presence of non‐activated CD19, and one which is independent of CD19. The involvement of CD19 in the first pathway was not due to the formation of putative CR2‐CD19 complexes. Both pathways were TAPA‐1 independent. This is the first demonstration that activated CR2 molecules can play a regulatory role in enzymatic function, such as phosphorylation, despite the absence of CD19 and TAPA‐1.
Monocyte activation: rapid induction of α1/β1 (VLA‐1) integrin expression by lipopolysaccharide and interferon‐γ
Authors: Rubio Miguel Angel , Sotillos Marisol , Jochems Gijs , Alvarez Vicente , Corbií Angel L. 
Published: March 2007

AbstractMonocytes play a key role in inflammation, tissue injury and remodelling and wound healing, and most monocyte effector functions are dependent on adhesive interactions. We have analyzed the changes in the pattern of β1 integrin expression that take place during monocyte activation and demonstrated that lipopolysaccharide (LPS) and interferon (IFN)‐γ specifically induce the expression of the α1/β1 integrin, which was detectable on the monocyte membrane as early as 12 h after monocyte activation. The up‐regulated α1/β1 expression was not dependent on monocyte adherence to solid surfaces, and Northern blot analysis revealed that LPS and IFN‐γ induce the α1 mRNA de novo. Monocyte deactivating cytokines such as interleukin (IL)‐4 or IL‐10, could only minimally inhibit the LPS‐ or IFN‐γ mediated up‐regulation of α1/β1, suggesting that cytokine release subsequent to monocyte activation does not play a major role in the integrin induction. Interestingly, the LPS‐induced expression of α1/β1 was found to be dependent on the redox state of the cell, since it was inhibited by antioxidants which also altered the morphological changes that take place during monocyte culture in vitro. The rapid induction of α1 in LPS‐activated monocytes suggests that α1/β1 might be involved not only in monocyte/extracellular matrix interactions during inflammatory reactions, but also in contributing to further monocyte activation and cytokine production during septic shock syndrome.
Characterization of thymic stromal‐derived lymphopoietin (TSLP) in murine B cell development in vitro
Authors: Ray Robert J. , Furlonger Caren , Williams Douglas E. , Paige Christopher J. 
Published: March 2007

AbstractB cell development is dependent on both direct interactions with stromal cells and their secreted cytokines. The precise mechanisms by which these interactions regulate B cell differentiation are currently unknown. We report here that a novel growth factor thymic stromal‐derived lymphopoietin (TSLP) can replace the activity of interleukin‐7 (IL‐7) in supporting B cell development in vitro. TSLP was found to promote the proliferation and differentiation of committed B220+ B cell progenitors from day 15 fetal liver. Phenotypic analysis of these cells revealed that they are at the pro‐B cell stage of differentiation and express cell surface markers characteristic of pro‐B cells cultured in IL‐7. TSLP can replace the activity of IL‐7 in supporting the progression of B lymphocytes from uncommitted bipotential precursors. In the absence of either TSLP or IL‐7, the progeny of cells that give rise to mature B lymphocytes fail to develop from these bipotential precursors. Moreover, TSLP can substitute for IL‐7 in supporting the sustained proliferative response exhibited by B cell progenitors from CBA/N mice. Together these results show that TSLP can replace the requirement for IL‐7 during in vitro B cell development.
Phenotypic and functional analysis of B lymphopoiesis in interleukin‐7‐transgenic mice: expansion of pro/pre‐B cell number and persistence of B lymphocyte development in lymph nodes and spleen
Authors: Mertsching Elisabeth , Grawunder Ulf , Meyer Valerie , Rolink Ton , Ceredig Rhodri 
Published: March 2007

AbstractTransgenic mice in which mouse interleukin (IL)‐7 cDNA is expressed under the control of the mouse major histocompatibility complex (MHC) class II (Eα) promoter develop a lymphoproliferative disease characterized by the early polyclonal expansion of T cells followed in many cases by the development of lymphomas of immature B cells. Here, we have analyzed B cell development in these transgenic mice. Phenotypic analysis using monoclonal antibodies to B220, IgM, IgD, c‐kit, IL‐7 receptor, MHC class II, AA4.1, CD19, CD23, CD25, CD40 and CD43 shows that B lymphopoiesis in the bone marrow is dramatically altered and the number of pro/pre‐B and immature B cells is significantly increased. Interestingly, pro/pre‐B and immature B cells persist in the spleens of adult transgenic mice and are also present in lymph nodes and blood. Cell cycle analysis of lymph node cells shows that subpopulations of developing B cells retain the cell cycle profiles of their bone marrow counterparts. Limiting dilution analysis shows that the number of clonable pre‐B cells is significantly increased and that at limiting dilution, growth of transgenic pre‐B cells is still dependent on exogenous IL‐7. Using semiquantitative polymerase chain reaction (PCR) and in situ hybridization, the level of IL‐7 transcripts in the spleen was found to decrease between 2 and 4 weeks in control mice with levels in transgenics mice being approximately 50 times greater. These transgenic mice represent an interesting model with which to study the effects of IL‐7 overexpression in the bonemarrow and raise interesting questions regarding the regulation of B lymphopoiesis in normal mice.
Human eosinophils express messenger RNA encoding RANTES and store and release biologically active RANTES protein
Authors: Ying Sun , Meng Qiu , Taborda‐Barata Luis , Corrigan Christopher J. , Barkans Julia , Assoufi Basil , Moqbel Redwan , Durham Stephen R. , Kay A. Barry 
Published: March 2007

AbstractEosinophils synthesize and store various cytokines with potential autocrine activity. We hypothesized that eosinophils synthesize and store RANTES, a CC chemokine with potent eosinophil chemotactic activity. Expression of RANTES mRNA in highly purified eosinophil populations was detected by reverse transcription followed by polymerase chain reaction analysis. In situ hybridization (ISH) with 35S‐labeled RANTES‐specific riboprobes showed that 6.8–10% of peripheral blood eosinophils obtained from atopic subjects expressed RANTES mRNA, increasing to 25% after incubation (16 h) with interferon(IFN)‐γ, but not ionomycin in vitro. Peripheral blood eosinophils also showed specific immunoreactivity with an anti‐RANTES monoclonal antibody, consistent with translation of the mRNA. By enzyme‐linked immunosorbent assay, blood eosinophils were shown to contain a median of 7300 pg (range 5200–8800) RANTES per 106 cells, of which a mean of 24% was released into culture supernatants after stimulation of the cells with serum‐coated particles in vitro. These culture supernatants exhibited eosinophil chemotactic activity which was inhibited (mean 68%) by a specific anti‐RANTES antibody. Sequential immunocytochemistry and ISH on biopsies obtained from allergen‐induced late‐phase cutaneous reactions showed that 55–75% of the infiltrating RANTES mRNA+ cells were EG2+ eosinophils. Allergen, but not diluent challenge, was also associated with a time‐dependent increase in the number of cells showing RANTES immunoreactivity. Of these cells, 55% were identified as eosinophils by morphological criteria. Thus, human eosinophils have the capacity to synthesize, store and secrete physiologically relevant quantities of RANTES, and may therefore be an important source of this chemokine in allergic inflammation.
Differences and similarities in the A2.1‐restricted cytotoxic T cell repertoire in humans and human leukocyte antigen‐transgenic mice
Authors: Wentworth Peggy A. , Vitiello Antonella , Sidney John , Keogh Elissa , Chesnut Robert W. , Grey Howard , Sette Alessandro 
Published: March 2007

AbstractHLA‐A2.1‐binding peptides (n = 38) were screened for immunogenicity with human peripheral blood mononuclear cells in cytotoxic T lymphocyte (CTL) induction experiments in vitro and with splenocytes from HLA‐A2.1/Kb transgenic mice following immunization in vivo. These data were compiled and analyzed to determine the level of overlap between the A2.1‐restricted CTL repertoire of A2.1/Kb‐transgenic mice and A2.1+ humans. In both humans and mice, a major histocompatibility complex affinity threshold of approximately 500 nM appears to determine the capacity of a peptide to elicit a CTL response. Good concordance between the human data in vitro and mouse data in vivo was observed with 85% of the high‐binding peptides, 58% of the intermediate binders, and 83% of the low/negative binders. Although some peptides immunogenic for mouse CTL but not for humans (and vice versa) could be identified, the data as a whole suggest an extensive overlap between T cell receptor repertoires of mouse and human CTL and support the use of HLA‐transgenic mice for the identification of potential human CTL epitopes.
Expression of gp40, the murine homologue of human epithelial cell adhesion molecule (Ep‐CAM), by murine dendritic cells
Authors: Borkowski Teresa A. , Nelson Andrew J. , Farr Andrew G. , Udey Mark C. 
Published: March 2007

AbstractDendritic cells (DC) can be distinguished from other antigen‐presenting cells (APC) by their morphology, motility and ability to initiate primary responses in naive T cells. Certain cell surface proteins (e.g. major histocompatibility complex antigens, co‐stimulatory/adhesion molecules and DEC205) are selectively expressed by DC, and may contribute to the potent APC activity of these leukocytes. As an outgrowth of studies of adhesion molecules expressed by epithelia and Langerhans cells (LC), we examined DC from murine epidermis and various lymphoid tissues for evidence of expression of gp40, a glycoprotein recently identified as the murine homologue of human epithelial cell adhesion molecule (Ep‐CAM). gp40 was detected on freshly‐obtained LC, cultured LC and LC that migrated from skin explants, as well as on keratinocytes. In skin‐associated lymph nodes, gp40 was selectively expressed by some DC in T cell‐dependent areas. DC‐enriched preparations from skin‐associated lymph nodes and spleen contained many cells that co‐expressed DC markers (CD11c and DEC205) and high levels of gp40. Lower levels of gp40 were present on DC from gut‐associated lymph nodes. These results demonstrate that the putative homophilic adhesion molecule gp40 is expressed by subpopulations of DC in selected tissues; we propose that gp40 expression may have functional consequences for DC.
Tepoxalin blocks neutrophil migration into cutaneous inflammatory sites by inhibiting Mac‐1 and E‐selectin expression
Authors: Zhou Lubing , Pope Barbara L. , Chourmouzis Erika , Fung‐Leung Wai‐Ping , Lau Catherine Y. 
Published: March 2007

AbstractInflammation is characterized by the migration of polymorphonuclear leukocytes from the vasculature into the tissue causing profound injury. Adhesion and migration of neutrophils across the vascular bed are governed by a series of complex events including cytokine/chemokine production which in turn orchestrates the temporal expression of a cohort of adhesion molecules mediating the migration. Many of these adhesion molecules and their inducers are under the control of inflammatory response transcriptional factors such as NFXB and AP‐1. Recently we showed tepoxalin, previously known as a dual cyclooxygenase/lipoxygenase (CO/LO) inhibitor, to be a potent inhibitor of NFXB‐induced transcription in vitro. In this study, we demonstrated that when administered in vivo, tepoxalin but not naproxen (a nonsteroidal anti‐inflammatory drug, NSAID) or zileuton (an LO inhibitior), effectively inhibits neutrophil migration into inflammatory sites in murine skin stimulated by either lipopolysaccharide (LPS) or tumor necrosis factor‐α. Immunohistochemical analysis indicates that 10–50 mg/kg of tepoxalin inhibits neutrophil migration. It also effectively blocks the up‐regulation of Mac‐1 (CD11b/CD18) on neutrophils. Quantitative polymerase chain reaction Mac‐1 analysis shows that LPS‐induced transcription of E‐selectin mRNA was dramatically suppressed by both 25 and 50 mg/kg of tepoxalin, whereas the level of ICAM‐1 was only affected by 50 mg/kg of tepoxalin. Since it has been documented that the expression of E‐selectin and Mac‐1 is regulated either directly or indirectly by the transcription factor NFXB, our studies provide in vivo evidence that tepoxalin is a potent inhibitor of NFXB‐mediated events in animal models and this novel molecular mechanism clearly defines it as a new class of anti‐inflammatory compounds.
Disease in the scurfy (sf) mouse is associated with overexpression of cytokine genes
Authors: Kanangat Sivadasan , Blair Patrick , Reddy Ramani , Deheshia Massoud , Godfrey Virginia , Rouse Barry T. , Wilkinson Erby 
Published: March 2007

AbstractThe murine X‐linked lymphoproliferative disease scurfy is similar to the Wiskott‐Aldrich syndrome in humans. Disease in scurfy (sf) mice is mediated by CD4+ T cells. Based on similarities in scurfy mice and transgenic mice that overexpress specific cytokine genes, we evaluated the expression of cytokines in the lesions of sf mice by Northern blotting, quantitative reverse‐transcription polymerase chain reaction (RT‐PCR) and by hybridization in situ. Overall, the phenotypic characteristics of scurfy disease correlated well with increased interleukin (IL)‐4 (lymphadenopathy), IL‐6 (B cell proliferation, hypergammaglobulinemia), IL‐7 (dermal inflammatory cell infiltration), and high levels of tumor necrosis factor‐α (wasting).
High doses of interleukin‐12 inhibit the development of joint disease in DBA/1 mice immunized with type II collagen in complete Freund's adjuvant
Authors: Hess Henry , Gately Maurice K. , Rüde Erwin , Schmitt Edgar , Szeliga Jacek , Germann Tieno 
Published: March 2007

AbstractCollagen‐induced arthritis (CIA) is an (autoimmune) joint disease readily elicited in DBA/1 mice by immunization with type II collagen (CII) emulsified with complete Freund's adjuvant. It is a destructive arthritis involving about 50% of the limbs and occurs with an incidence of 70% to 100%. In this study we evaluated the effect of mouse recombinant interleukin‐12 (mrIL‐12) on CIA. Administration of mrIL‐12 at high doses (1 μg/mouse, daily) for 2 or 3 weeks delayed the onset and reduced the incidence of CIA. Furthermore, the severity of CIA was much milder and in most cases restricted to single digits of the paws. Short‐term administration of high doses of IL‐12 exerted some, but less pronounced, disease‐suppressing effect. In contrast, 10‐fold lower doses of IL‐12 given during the first 3 weeks, or high doses of IL‐12 administered therapeutically proved to be ineffective. Only those regimens of IL‐12 treatment that ameliorated CIA were associated with a down‐regulation of the CII‐specific antibody response. A strong inhibition of CII‐specific IgG1 antibodies (10‐ to 20‐fold) and a moderately (2‐ to 6‐fold) suppressed IgG2b response was observed, whereas the level of CII‐specific IgG2a antibodies remained high. Taken together, the results indicate that some initial events in the induction of CIA in DBA/1 mice injected with CII emulsified with CFA are suppressed by treatment with high doses of IL‐12.
Lack of intermediate‐affinity interleukin‐2 receptor in mice leads to dependence on interleukin‐2 receptor α, β and γ chain expression for T cell growth
Authors: Chastagner Patricia , Moreau Jean‐Louis , Jacques Yannick , Tanaka Toshiyuki , Miyasaka Masayuki , Kondo Motonari , Sugamura Kazuo , Thèze Jacques 
Published: March 2007

AbstractAn interleukin (IL)‐4 dependant mouse T cell clone 8.2 derived from an IL‐2‐dependent T cell line was characterized. As measured by flow cytometric analysis and Northern blotting, it expresses IL‐2 receptor β (IL‐2Rβ) and γ (IL‐2Rγ) chains, but has lost expression of IL‐2 receptor α chain (IL‐2Rα). To investigate the properties of the mouse IL‐2Rβγ complex and the role of IL‐2Rα gene expression, this clone was further studied. T cell clone 8.2 has lost the capacity to bind 125I‐labeled human IL‐2 under experimental conditions able to detect intermediate‐affinity IL‐2R in human cells. Mouse IL‐2 is unable to block the binding of mAb TMβ1 to 8.2 cells. Under the same experimental conditions, mouse IL‐2 blocks the binding of TMβ1 to C30‐1 cells expressing the IL‐2αβγ complex. Since TMβ1 recognizes an epitope related to the IL‐2 binding site of IL‐2Rβ, these results can be taken as a demonstration that mouse IL‐2Rβγ does not bind mouse IL‐2. Furthermore, T cell clone 8.2 does not proliferate in response to recombinant mouse or human IL‐2. On the other hand, T cell transfectant lines expressing heterospecific receptors made of the human IL‐2Rβ and mouse IL‐2Rγ chains bind 125I‐labeled human IL‐2 and proliferate in response to IL‐2. This establishes the difference between mouse and human IL‐2Rβ chains. Transfection of T cell clone 8.2 with human IL‐2Rα genes restores their capacity to proliferate in response to IL‐2. In addition, all transfectants grown in IL‐2 express the endogeneous mouse IL‐2Rα chain. When grown in IL‐4, the endogeneous mouse IL‐2Rα gene remains silent in all these transfectants. These results show that, contrary to the human, the mouse does not express an intermediate‐affinity IL‐2R. Expression of the IL‐2Rα gene is therefore required for the formation of the functional IL‐2R in mice.
Self‐renewal of B‐1 lymphocytes is dependent on CD19
Authors: Krop Ian , De Fougerolles Antonin R. , Hardy Richard R. , Allison Michael , Schlissel Mark S. , Fearon Douglas T. 
Published: March 2007

AbstractThe B‐1 subset of B lymphocytes is maintained by self‐renewal of mature cells, and this process may involve signaling through membrane immunoglobulin (mIg). We determined whether CD19, a membrane protein that co‐stimulates B cells by mIg, has a role in this process. Pre‐natal treatment of mice with 1D3, a rat anti‐mouse CD19 monoclonal antibody, down‐regulated CD19 expression and reduced by sixfold the number of B‐1a cells at birth; B‐2 cells were relatively unaffected. Prolonged treatment of adult mice with 1D3 caused the loss of approximately 2% per day of peritoneal B‐1a cells, without diminishing the recovery of splenic B‐2 cells. The loss of B‐1a cells was associated with inhibition of their replication rather than with accelerated turnover. Therefore, CD19 is involved in the development and self‐renewal of B‐1a cells, perhaps through its ability to amplify signaling through mIgM.