bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polyinosinic acid: polycytidylic acid promotes T helper type 1‐specific immune responses by stimulating macrophage production of interferon‐α and interleukin‐12
Authors: Manetti Roberto , Annunziato Francesco , Tomasevic Ljiljana , Giannò Valeria , Parronchi Paola , Romagnani Sergio , Maggi Enrico 
Published: March 2007

AbstractThe effects exerted on the development in vitro of Dermatophagoides pteronyssinus group I (Der p I)‐specific T cell lines and T cell clones by addition of polyinosinic acid: polycytidylic acid (poly I:C) in lymphocyte bulk culture were examined. Der p I‐specific T cell lines generated in presence of poly I:C exhibited reduced ability to produce interleukin (IL)‐4 and IL‐5 and developed into Der p I‐specific CD4+ T cell clones showing a T helper (Th) type 0 or Th1, instead of Th0/Th2 cytokine profile. This effect was prevented by addition to lymphocyte bulk cultures of a mixture of antibodies specific for interferon (IFN)‐α and IL‐12, whereas the addition of anti‐IFN‐α or anti‐IL‐12 antibody alone was uneffective. Poly I:C also showed the ability to stimulate the production of noticeable amounts of both IFN‐α and IL‐12 by human monocytes. Taken together, these data suggest that poly I:C is a Th1‐inducing agent whose activity is mediated by its ability to stimulate the production of IFN‐α and IL‐12 by monocytes.
Down‐modulation of CD4+ T helper type 2 and type 0 cells by T helper type 1 cells via Fas/Fasligand interaction
Authors: Hahn Sinuhe , Stalder Thomas , Wernli Marion , Bürgin Diana , Tschopp Jürg , Nagata Shigekazu , Erb Peter 
Published: March 2007

AbstractFas was recently demonstrated to be the major target molecule engaged by CD4+ cytolytic T lymphocytes (CTL). We examined Fas expression on various cloned T cell subpopulations and their susceptibility to lysis by CD4+ or CD8+ CTL. A reciprocal relationship in Fas and Fas‐ligand expression was observed in CD4+ T helper (Th)1‐ and Th2‐type clones, and Fas mRNA was predominantly detected in Th2 clones, whereas Fas‐ligand mRNA was principally found in Th1 clones. The two Th0 clones tested expressed both Fas and Fas‐ligand, but only one exhibited cytolytic activity, whereas both were sensitive to CD4‐mediated lysis. A functional consequence of the inverse Fas‐Fas‐ligand expression pattern was that Th2 and Th0 cells were sensitive to lysis by both Th1 CD4+ CTL and a CD8+ CTL clone in a Fas‐dependent manner. These results suggest that cytolytic CD4+ Th1 cells may play an immunomodulatory role, regulating a Th2/Th0 response by Fas‐mediated lysis.
Exogenous human immunodeficiency virus type‐1 Tat protein selectively stimulates a phosphatidylinositol‐specific phospholipase C nuclear pathway in the Jurkat T cell line
Authors: Zauli Giorgia , Previati Marizio , Caramelli Elisabetta , Bassini Alessandra , Falcieri Elisabetta , Gibellini Davide , Bertolaso Lucia , Bosco Domenico , Robuffo Iole , Capitani Silvano 
Published: March 2007

AbstractWe investigated the effect of extracellular Tat protein of human immunodeficiency virus‐type 1 (HIV‐1) on the phosphatidylinositol (PI) cycle, which represents a major signal transduction pathway in lymphoid cells. Recombinant Tat, recombinant HIV‐1 p24 and cross‐linked anti‐CD3 monoclonal antibody (mAb) were added in culture for 1–60 min to Jurkat lymphoblastoid CD4+ T cells. The stimulation of T cell receptor by cross‐linked anti‐CD3 mAb resulted in a rapid increase of the phosphatidylinositol‐specific phospholipase C (PI‐PLC) activity in whole cell lysates. On the other hand, Tat protein, either alone or in combination with anti‐CD3 mAb, showed little effect on the PI turnover of whole cell extracts. Tat, however, selectively stimulated a nuclear‐specific PI‐PLC with a peak of activity after 30 min from the addition in culture to Jurkat cells. Interestingly, this time corresponded to that required for the uptake and nuclear localization of recombinant Tat protein, as demonstrated by electron microscope immunocytochemistry experiments with anti‐Tat mAb. Moreover, exogenous Tat reached the nucleus of Jurkat cells in a bioactive form, as shown in a HIV‐1 long terminal repeat‐chloramphenicol acetyl transferase transactivation assay. The specific increase of a nuclear PI‐PLC activity was further demonstrated by the ability of Tat to stimulate PI turnover also when added directly to isolated nuclei. As a whole, these data demonstrate that Tat selectively stimulates a nuclear polyphosphoinositide hydrolysis, which appears to be independent of the cellular PI turnover. The relevance of these findings for a better understanding of the biological functions of extracellular Tat is discussed.
Polymorphonuclear granulocytes enhance lipopolysaccharide‐induced soluble p75 tumor necrosis factor receptor release from mononuclear cells
Authors: Lien Egil , Liabakk Nina‐Beate , Johnsen Ann‐Charlotte , Nonstad Unni , Sundan Anders , Espevik Terje 
Published: March 2007

AbstractLipopolysaccharide (LPS), a part of the Gram‐negative bacteria cell wall, is a potent inducer of tumor necrosis factor (TNF). TNF is an important mediator in Gram‐negative infections such as meningococcal septic shock, but its harmful action can be prevented by the natural occurring soluble (s) TNF receptors (sTNFR) sp55 and sp75. In this study, the effect of LPS on release of sTNFR was investigated. First, we found a selective increase in human whole‐blood sp75 TNFR levels following LPS stimulation, accompanied by no increase in sp55. Separating the different blood cell populations, mononuclear cells (PBMC) selectively released sp75 upon LPS stimulation, while LPS induced a minor increase in sp75 release from polymorphonuclear granulocytes. Interestingly, in co‐cultures of PBMC and granulocytes, the release of LPS‐induced sp75 TNFR was enhanced. Second, adherent monocytes were also found to selectively release sp75 TNFR upon LPS stimulation, where Neisseria meningitidis LPS was found to be 100‐1000 times more potent in inducing sp75 release than Escherichia coli LPS. Using flow cytometry, the monocyte membrane distribution of both TNFR were found to be increased after LPS stimulation. Third, human umbilical vein endothelial cells selectively released sp55 TNFR after stimulation with LPS. We conclude that mononuclear and endothelial cells might be the main sources of soluble p75 and p55 TNFR, respectively, observed in Gramnegative sepsis, although these receptors are released in vivo more rapidly than they are in vitro.
In vitro cultured stromal cells from human tonsils display a distinct phenotype and induce B cell adhesion and proliferation
Authors: Lisignoli Gina , Monaco Maria C. G. , Facchini Andrea , Toneguzzi Stefania , Cattini Luca , Hilbert David M. , Lavaroni Stefano , Belvedere Ornella , Degrassi Alberto 
Published: March 2007

AbstractPeripheral lymphoid tissues contain a fibroblastic cell type referred to as stromal cells or reticulum cells which interact with lymphocytes as part of the lymphoid microenvironment. After isolation from human tonsils and expansion in vitro we analyzed the surface phenotype, extracellular matrix components, cytoskeletal products, cytokine production, binding and functional interaction with B lymphocytes of in vitro cultured stromal cells (HTSC) both in resting condition and after activation with tumor necrosis factor (TNF)‐α and interferon (IFN)‐γ. Our results show that HTSC do not express specific myeloid, lymphoid, endothelial or epithelial markers. HTSC express CD54 (ICAM‐1), CD49a (VLA‐1), CD49b (VLA‐2), CD49c (VLA‐3), CD49e (VLA‐5), CD49f (VLA‐6), CD29, CD51, CD44 and produce vinculin, β‐tubulin, α‐actin, vimentin, fibronectin, laminin and collagen types I, III and IV. Activation of HTSC up‐regulated CD54 (ICAM‐1) and induced HLA‐DR and CD106 (VCAM‐1).HTSC constitutively produce interleukin (IL)‐6 which is enhanced upon activation with TNF‐α. IL‐8 and granulocyte/macrophage colony‐stimulating factor are detected only in the supernatants of activated HTSC. Reverse transcriptase polymerase chain reaction analysis revealed that HTSC display mRNA for IL‐1α, leukemia inhibitory factor and IL‐7. The adhesion of tonsillar B lymphocytes to activated HTSC is mediated by CD11a/CD18 and CD54. Furthermore, HTSC can induce maximal proliferation of IL‐2‐activated B lymphocytes cocultured in direct cell‐cell contact with HTSC. These results clearly distinguish in vitro cultured HTSC from common fibroblasts and other non‐lymphoid elements present in the lymphoid parenchyma, such as follicular dendritic cells, and show that HTSC actively participate in the lymphoid microenvironment. In vitro cultures of HTSC could therefore be a useful model system for detailed analysis of the interactions between stromal cells and lymphocytes under physiological and pathological conditions.
Calcium‐dependent lectin activity with novel distribution on thymocyte subsets
Authors: Mallett Susan , Rosen Steven D. , Hyun William 
Published: March 2007

AbstractIn this study we use carbohydrate probes to search for novel cell surface lectins in the immune system. Many carbohydrate binding proteins are members of the C‐type lectin superfamily, whose ligand binding is dependent on calcium. To identify potential new members of this superfamily, fluorescein‐conjugated carbohydrate polymers were used to probe for calcium‐dependent cell surface binding. This approach offers advantages over the use of monoclonal antibody probes since only carbohydrate binding proteins would be identified. We have identified a cell surface lectin, referred to as thy‐lec, detected by the probe fucoidan‐fuorescein isothiocyanate. This calcium‐dependent lectin has a novel distribution on thymocyte subsets. It is present on the surface of immature CD4+8+ and on large, cycling CD4−8− cells and CD8+4− cells, but not on small, mature phenotype CD8+4− or CD4+8− thymocytes. This lectin is not found on mature T cells or other leukocytes in lymph nodes, spleen or bone marrow. It is proposed that this novel cell surface has a function in the maturation of T cells in the thymus.
Autoreactive T cell specificity in autoimmune hemolytic anemia of the NZB mouse
Authors: Perry Frances E. , Barker Robert N. , Mazza Graziella , Day Michael J. , Wells Angela D. , Shen Chia‐Rui , Schofield Ann E. , Elson Christopher J. 
Published: March 2007

AbstractSplenic T cells from Coombs'‐positive New Zealand Black (NZB) mice proliferated consistently in vitro in response to the integral red blood cell (RBC) membrane protein Band 3, the antigen previously shown to be the target for the pathogenic RBC autoantibodies. The responding cells predominantly express CD4 and the proliferative response is blocked by antibodies to the NZB major histocompatibility complex class II but not by antibodies to an irrelevant H‐2 haplotype. NZB splenic T cells also proliferated in response to the internal membrane skeleton protein spectrin. By contrast, T cells from BALB/c and DBA2 mice, which bear the same H‐2 haplotype as NZB mice, but which do not develop autoimmune hemolytic anemia (AIHA), fail to respond to Band 3. It is considered that these results support the hypothesis that Band 3‐reactive T cells provide help for the production of pathogenic anti‐Band 3 autoantibodies in NZB mice. T cells from Coombs'‐negative NZB mice as young as 3 weeks old proliferated in response to Band 3; moreover, the RBC from Coombs'‐negative mice bore elevated levels of autoantibody as judged by a sensitive direct enzyme‐linked anti‐globulin test. Thus, the pathology of AIHA develops at a much earlier age than was thought previously.
Expression of the common cytokine receptor γ chain by murine dendritic cells including epidermal Langerhans cells
Authors: Mohamadzadeh Mansour , Ariizumi Kiyoshi , Sugamura Kazuo , Bergstresser Paul R. , Takashima Akira 
Published: March 2007

AbstractThe common cytokine receptor γ chain (γc) is an indispensable component of interleukin (IL)‐2, IL‐4, IL‐7, IL‐9, and IL‐15 receptors, and its expression has been detected in several leukocyte populations, including T cells, B cells, monocytes, natural killer cells, and neutrophils. The purpose of this study was to determine whether γc receptors are expressed by dendritic cells (DC). Constitutive γc mRNA expression was observed by reverse transcription polymerase chain reaction and/or Northern blotting for: (a) Ia+ epidermal Langerhans cells (LC), (b) 4F7+ splenic DC, (c) granulocyte/macrophage colony‐stimulated factor‐propagated bone marrow‐derived DC, and (d) the epidermal‐derived DC line, XS52, which retains important functions of epidermal LC. Exposure of XS52 cells to recombinant IL‐4 induced a rapid up‐regulation of c‐myc mRNA expression, and this IL‐4‐dependent signaling was blocked almost completely by anti‐γc monoclonal antibody (mAb) TUGm2 in a soluble form. Moreover, c‐myc up‐regulation was inducible in XS52 cells by the same mAb in an immobilized form. These results imply that molecules recognized by this antibody (i.e. γc receptors) are expressed on XS52 cell surfaces. We thus conclude that DC express functional γc receptors, which then mediate cytokine‐dependent regulation of DC functions.
Non‐tolerant B cells cause autoimmunity in anti‐CD8 IgG2a‐transgenic mice
Authors: Battegay Manuel , Fiedler Petra , Kalinke Ulrich , Brombacher Frank , Zinkernagel Rolf M. , Peter Hans‐Hartmut , Köhler Georges , Eibel Hermann 
Published: March 2007

AbstractUsing a pair of γ2a/x immunoglobulin genes, transgenic mice were generated to study tolerance induction in B cells that express IgG2a autoantibodies. The transgenic IgG2a specifically binds CD8 α chains of the CD8.2 allotype expressed on the surface of CD8+ T cells, but not CD8 molecules expressed by the CD8.1 allele. Thus, IgG2a transgenic mice expressing the CD8.1 allele were used as controls to monitor B cell development and mice expressing CD8.2 were used to study B cell tolerance. Both types of mice showed transgenic γ2a expression on the surface of B cells. Expression of endogenous heavy chain alleles was strongly inhibited in immature B cell subsets, whereas mature B cells co‐expressed transgenic γ2a and endogenous IgM/D. The transgenic x chain expression leads only to partial allelic exclusion of endogenous light chains. B cells that express high levels of transgenic CD8.2‐specific IgG2a were identified using soluble CD8‐Ig. In CD8.1+ and in CD8.2+ mice, we found no differences in expression and maturation of transgenic anti‐CD8.2 IgG2a+ B cells. High levels of serum anti‐CD8.2 IgG2a antibodies led to the elimination of CD8+ T cells, causing a severe defect in cytotoxic immune responses. These results show that tolerance induction is incomplete in the CD8.2+ mice, either because IgG2a+ B cells are resistant to censoring mechanisms or because the secreted CD8‐specific IgG2a antibodies render the CD8 autoantigen inaccessible to the B cells. This contrasts strongly with the efficient induction of B cell tolerance in mice expressing anti‐CD8.2 IgM autoantibodies.
Biological function and distribution of human interleukin‐12 receptor β chain
Authors: Wu Chang‐You , Warrier Rajeev R. , Carvajal Daisy M. , Chua Anne O. , Minetti Lisa J. , Chizzonite Richard , Mongini Patricia K. A. , Stern Alvin S. , Gubler Ueli , Presky David H. , Gately Maurice K. 
Published: March 2007

AbstractWe previously described the cloning of a cDNA encoding an interleukin‐12 receptor (IL‐12R) subunit, designated β, that bound IL‐12 with low affinity when expressed in COS cells. We now report that a pair of monoclonal antibodies (mAb), 2B10 and 2.4E6, directed against different epitopes on the IL‐12Rβ chain, when used in combination, strongly inhibited IL‐12‐induced proliferation of activated T cells, IL‐12‐induced secretion of interferon‐γ by resting peripheral blood mononuclear cells (PBMC), and IL‐12‐mediated lymphokine‐activated killer cell activation. The mAb had no effect on lymphoblast proliferation induced by IL‐2, −4, or −7. Thus, the IL‐12Rβ chain appears to be an essential component of the functional IL‐12R on both T and natural killer (NK) cells. We previously observed that high affinity IL‐12R were expressed on activated T and NK cells, but not B cells. Studies using flow cytometry and reverse transcription‐polymerase chain reaction analysis showed that IL‐12Rβ chain was expressed on several human T, NK, and (surprisingly) B cell lines, but not on non‐lymphohematopoietic cell lines. The Kit225/K6 (T cell) and SKW6.4 (B cell) lines were found to express the greatest amounts of IL‐12Rβ chain (800–2500 sites/cell); however, Kit225/K6 but not SKW6.4 cells bound IL‐12. Similar to SKW6.4 B cells, activated tonsillar B lymphocytes expressed IL‐12Rβ chain but, consistent with previous results, did not display detectable IL‐12 binding. Likewise, up to 72% of resting PBMC from normal volunteer donors expressed IL‐12Rβ, but did not bind measurable amounts of IL‐12. These results indicate that expression of IL‐12Rβ is essential, but not sufficient, for expression of functional IL‐12R. We speculate that expression of functional, high‐affinity IL‐12R may require the presence of a second subunit that is more restricted in its expression than IL‐12Rβ.
Co‐localization of β2‐microglobulin and IgG in human placental syncytiotrophoblasts
Authors: Kristoffersen Einar K. , Matre Roald 
Published: March 2007

AbstractThe fetal syncytiotrophoblast cells in close contact with maternal blood circulation apparently lack surface expression of HLA molecules, including the HLA light chain β2‐microglobulin. This is thought to contribute significantly to a successful pregnancy. We find that syncytiotrophoblasts do express β2‐microglobulin. β2‐microglobulin is primarily localized intracellularly in apical granules, and co‐localize with human IgG. The origin and function of syncytiotrophoblast β2‐microglobulin is unknown, but its localization in the syncytiotrophoblasts may implicate β2‐microglobulin in the transplacental transport of IgG in conjunction with a recently identified class I HLA‐like receptor for IgG/Fc. Alternatively, β2‐microglobulin may associate with a hitherto unidentified class I HLA molecule.
A monoclonal antibody, 3/22, to rabbit CD11c which induces homotypic T cell aggregation: evidence that ICAM‐1 is a ligand for CD11c/CD18
Authors: Blackford Jeanette , Reid Hugh W. , Pappin Darryl J. C. , Bowers Florence S. , Wilkinson J. Michael 
Published: March 2007

AbstractThe rabbit CD11c molecule has been characterized by use of a new monoclonal antibody, mAb 3/22. Expression of the p150,95 integrin (CD11c/CD18) has been shown by flow cytometry and immunohistochemistry to be restricted to monocytes, macrophages, dendritic cells and a small population of lymphocytes in peripheral blood. No expression on neutrophils could be demonstrated. Incubation of the newly derived CD8+ T cell line, BJ/873, with mAb 3/22 causes homotypic aggregation, which has been shown to be a cell surface event that is not dependent on intracellular signaling or on receptor cross‐linking. Inhibition studies show that the ligands responsible for this aggregation are CD11c/CD 18 and ICAM‐1, both of which are expressed on BJ/873. One other rabbit T cell line, K34, that also expresses p150,95 and ICAM‐1, shows a similar aggregation response when stimulated with 3/22. Cell lines that express p150,95 but not ICAM‐1 do not aggregate. These observations suggest that ICAM‐1 is a ligand for activated p150,95.
Nitric oxide‐mediated suppression of T cell responses during Trypanosoma brucei infection: soluble trypanosome products and interferon‐γ are synergistic inducers of nitric oxide synthase
Authors: Sternberg Jeremy M. , Mabbott Neil A. 
Published: March 2007

AbstractAfrican trypanosome infections result in lymphocyte unresponsiveness and anemia in the mammalian host. In murine infections, these effects are mediated by suppressor macrophages releasing nitric oxide (NO). We investigated the mechanism of activation of macrophages to produce NO during trypanosomiasis in vitro. A soluble component of trypanosome lysates induced NO synthesis in peritoneal macrophage cultures only when the macrophages were co‐stimulated with interferon‐gamma (IFN‐γ). The macrophage‐activating factor was also released in a soluble form by live bloodstream‐form trypanosomes, but not procyclic trypanosomes. When splenocyte cultures were exposed to IFN‐γ and trypanosomes, an NO‐dependent suppression of T cell proliferation occurred. This is similar to the suppression observed in the spleens of trypanosome‐infected mice, suggesting that a combination of trypanosome‐released macrophage‐activating factors and IFN‐γ are a trigger of immune dysfunction in trypanosomiasis.
Different cytokines regulate antigen uptake and presentation of a precursor dendritic cell line
Authors: Lutz Manfred B. , Aßmann Caroline U. , Girolomoni Giampiero , Ricciardi‐Castagnoli Paola 
Published: March 2007

AbstractLangerhans cells (LC) and dendritic cells (DC) need to be activated in order to perform their antigen‐presenting function. In this study, we explored the influence of cytokines on the uptake and presentation of protein antigens by the retrovirally immortalized myeloid cell line FSDC. This cell line was generated from mouse fetal skin and was previously shown to have the characteristics of early DC precursors. Both FSDC and bone marrow‐derived DC (BM‐DC) were more effective in the pinocytosis of FITC‐conjugated ovalbumin (FITC‐OVA) and dextran (FITC‐DX) than B cells or macrophages. Pretreatment of FSDC with granulocyte/macrophage colony‐stimulating factor (GM‐CSF) ± interleukin (IL)‐4 enhanced the pinocytic uptake of FITC‐OVA and FITC‐DX, but did not induce antigen‐presenting capacity. In contrast, untreated FSDC or FSDC pre‐incubated with GM‐CSF ± IL‐4 suppressed T cell responses. Treatment of FSDC with IFN‐γ reduced pinocytosis but increased the expression of MHC and co‐stimulatory/adhesion molecules and promoted efficient presentation of OVA protein or peptide to the specific DO11.10 T cell hybridoma or to naive CD4+ T cells from DO11.10 TCR‐transgenic mice. The results suggest that antigen uptake and antigen presentation in DC are regulated by different cytokine signals provided by the surrounding tissue.