bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fluids from immune privileged sites endow macrophages with the capacity to induce antigen‐specific immune deviation via a mechanism involving transforming growth factor‐β
Authors: Wilbanks Garth A. , Wayne Streilein J. 
Published: March 2007

AbstractThe eye, brain, and fetoplacental unit within the pregnant uterus are immunologically privileged sites that contain unique fluids with suspected immunoinhibitory properties. Aqueous humor, which is normally present within the anterior chamber (AC) of the eye, has been shown to suppress antigen‐driven T cell activation, and to contain significant amounts of transforming growth factor β‐2 (TGF‐β). Antigens injected into the AC of normal mice induce a deviant form of systemic immunity, termed anterior chamber‐associated immune deviation (ACAID), which is characterized by a selective inability to display antigen‐specific delayed hypersensitivity. It has recently been reported that eye‐derived macrophages appear in the blood following AC injection of a soluble antigen, and that these cells can induce antigen‐specific ACAID when injected into naive, syngeneic recipients. Moreover, antigen‐pulsed peritoneally derived macrophages that are exposed in vitro to aqueous humor, supernatants of cultured iris and ciliary body cells (I/CD), or TGF‐β have been found to assume ACAID‐inducing properties. In the present experiments, amniotic fluid and cerebrospinal fluid from mice, rats and humans, as well as supernatants from cultured I/CB cells, have been examined for their capacity to confer ACAID‐inducing properties on peritoneal macrophages. It was found that each of these biologic fluids, but neither normal mouse serum nor rat thoracic duct lymph, was able to endow antigen‐pulsed peritoneal macrophages with ACAID‐inducing properties. Moreover, fluids from these immune privileged sites were found to contain latent and/or active TGF‐β, as determined by bioassay, using neutralizing anti‐TGF‐β antibodies. It is concluded (a) that the immune privileged states of the eye, the brain, and the fetoplacental unit share common features, and possess unique fluids with a similar capacity to force macrophages to present antigens in a “deviant” manner and (b) that this capacity is mediated, at least in part, by TGF‐β. These results are discussed in terms of the potential physiologic and pathophysiologic significance of immune privilege in these three specialized tissues.
Does co‐aggregation of the CD45 and CD3 antigens inhibit T cell antigen receptor complex‐mediated activation of phospholipase C and protein kinase C?
Authors: Shivnan Emer , Biffen Mark , Shiroo Masahiro , Pratt Edward , Glennie Martin , Alexander Denis 
Published: March 2007

AbstractThe binding of agonistic monoclonal antibodies (mAb) to the CD3 antigen in T cells induces a rapid increase in tyrosine phosphorylation, inositive phosphate (IP) production, a rise in intracellular calcium and protein kinase C (PKC) activation. These intracellular signals have been implicated in the control of interleukin‐2 and interleukin‐2R receptor gene expression, thereby regulating T cell proliferation. Previous studies have shown that co‐ligation of the CD45 and CD3 antigens inhibits CD3‐induced tyrosine phosphorylation, IP production, calcium signals and T cell proliferation. It has therefore been suggested that the CD45 antigen uncouples the T cell receptor (TcR) from mitogenic signal pathways. In this study co‐ligation of the CD3 and CD45 antigens with precisely constructed bispecific mAb did not inhibit CD3‐induced T cell proliferation, IP production, calcium signals, diacylglycerol production or PKC activation. Furthermore, co‐ligation of CD3 and CD45 antigens already cross‐linked with IgM mAb did not lead to inhibition of CD3‐induced calcium signals. Inhibitions of CD3‐induced intracellular signals were observed following co‐ligation of IgG CD45 and CD3 mAb with anti‐IgG F(ab')2 fragments. However, comparable inhibitions were also noted following co‐ligation of CD3 with other abundant cell‐surface antigens such as CD5 and LFA‐1, and inhibitions were only observed when the CD3 mAb used required cross‐linking to induce signals. These results suggested that the inhibitory effects of CD45 IgG mAb were not specific and were caused by the prevention of CD3‐CD3 cross‐linking following CD3 antigen co‐ligation with other cell surface molecules. These findings are inconsistent with a specific inhibitory role for the CD45 phosphotyrosine phosphatase in uncoupling the TcR from mitogenic signal pathways.
Antibody binding to a collagen type‐II epitope gives rise to an inhibitory peptide for autoreactive T cells
Authors: Burkhardt Harald , Yan Tan , Bröker Barbara , Beck‐Sickinger Annette , Holmdahl Rikard , von der Mark Klaus , Emmrich Frank 
Published: March 2007

AbstractIt is well documented that antigen recognition by T cells requires small peptides which are generated by protein cleavage in antigen‐presenting cells. These peptides have to associate with major histocompatibility complex (MHC) molecules in order to be recognized. An inhibitory peptide may bind to the same site of the MHC‐encoded protein but is not recognized by the T cell. Here we describe a stimulatory and an inhibitory peptide sequence within human collagen type II (CII) as defined by means of the same autoreactive human T cell clone. Most interestingly, the inhibitory peptide is not generated by regular processing in peripheral blood mononuclear cells but only in the presence of an antibody that binds to the same domain and thereby seems to protect the inhibitory sequence. This finding may indicate that certain autoantibodies have the potential to block autoreactive T cells with specificity for a distinct epitope on the same antigen.
Expression of the adhesion molecules ICAM‐1 and ICAM‐2 on tumor cell lines does not correlate with their susceptibility to natural killer cell‐mediated cytolysis: evidence for additional ligands for effector cell β2 integrins
Authors: Akella Rama , Hall Robert E. 
Published: March 2007

AbstractThe LFA‐1 molecule (CD11a/CD18), a member of the leukocyte (β2) integrin subfamily of the integrin supergene family, has been shown to subserve important function(s) in natural killer (NK) and lymphokin‐activated killer (LAK) effector cells based on monoclonal antibody inhibition and other studies. Presently, two cellular ligands for LFA‐1 have been identified, termed ICAM‐1 and ICAM‐2. In this study, we have examined the role of target cell ICAM‐1 (CD54) and ICAM‐2 in NK‐mediated target lysis. Using a panel of tumor target cell lines, ICAM‐1 surface protein and transcript expression did not correlate with sensitivity to NK lysis. Compared to ICAM‐1, ICAM‐2 transcript expression was very low or undetectable in tumor cell targets, and also did not correlate with sensitivity to NK lysis. ICAM‐1+ K562 cells and K562 cells which were rendered surface ICAM‐1− with an antisense oligonucleotide were equally sensitive to NK lysis. Finally, human ICAM‐1− P815 cells were stably transfected with the human ICAM‐1 gene, and both ICAM‐1− P815 (wild type) and ICAM‐1+ stable transfectants were equally insensitive to NK lysis. These studies provide evidence that ICAM‐1 and ICAM‐2 are not important target cell ligands for NK effector cell LFA‐1 and that other target cell ICAM may exist.
Ipr T cells vaccinate against lupus in MRL/lpr mice
Authors: de Alborán Ignacio M. , Gutierrez José C. , Gonzalo José A. , Andreu José L. , Marcos Miguel A. R. , Kroemer Guido , Martínez‐A Carlos 
Published: March 2007

AbstractMRL/MP‐lpr/lpr mice are homozygous for the lpr mutation that results in the accumulation of phenotypically abnormal cells (CD3+CD4+CD8−) in all lymphoid issues. Although no major abnormalities in the T cell receptor repertoire expressed by such lpr cells have been reported, the lpr mutation is a major disease‐accelerating factor. Finally, intravenous administration of irradiated lpr cells recovered from the hyperplastic lymph nodes of adult diseased animals to young MRL/Mp‐lpr/lpr mice resulted in a highly significant amelioration of disease parameters. This “T cell vaccination” approach resulted in a selective depletion of cells expressing products of the Vβ8.2 subfamily among lymph node T cells, in addition to eliciting a surge in peripheral T cells capable of conferring disease protection in adoptive transfer experiments. Thus, a strategy aimed at specifically reducing the frequency of lpr cells proved successful in mitigating the autoimmune process. These findings add to the involvement of lpr cells in the autoimmune process and constitute the first report that T cell vaccination may be beneficial to a spontaneously occurring autoimmune disease.
Phenotypical and biochemical characterization of a variant CD45R expression pattern in human leukocytes
Authors: Schwinzer Reinhard , Schraven Burkhart , Kyas Urte , Meuer Stefan C. , Wonigeit Kurt 
Published: March 2007

AbstractAs a result of a regulatory polymorphism a variant pattern of CD45R expression can be found in 8% of healthy individuals. We have previously reported that all resting T cells of these individuals react with CD45RA monoclonal antibodies (mAb) that are directed to the high‐molecular mass isoforms (220 and 205 kDa) of the leukocyte common antigen (CD45). In addition, their T cells remain CD45RA+ after in vitro activation. In this report we studied the regulatory CD45R polymorphism in more detail. Flow cytometry studies revealed that CD45RA antigens are weakly expressed on normal monocytes but are absent from granulocytes. In individuals displaying the variant CD45R pattern both monocytes and granulocytes were CD45RA+. In controls and variant T cells CD45RA mAb precipitated two chains with molecular masses of about 220 and 205 kDa. In activated T cells from controls (CD45RA−) neither p220 nor the p205 chain of CD45RA could be detected. However, activated T cells from variant individuals (CD45RA+) did not express p220 but expressed p205 of CD45RA. These data indicate that there is a failure to down‐regulate p205 CD45RA in individuals displaying the variant CD45R expression pattern. Since their T cells lost p220 CD45RA during activation the data also suggest that the two isoforms detected by CD45RA mAb can be regulated independently.
Molecular cloning of a novel member of the immunoglobulin gene superfamily homologous to the polymeric immunoglobulin receptor
Authors: Jackson David G. , Hart Derek N. J. , Starling Gary , Bell John I. 
Published: March 2007

AbstractThe CMRF35 monoclonal antibody recognizes a cell membrane antigen present on the surface of monocytes, neutrophils, a proportion of peripheral blood T and B lymphocytes and lymphocytic cell lines. Initial studies with CMRF35 suggested an unusual pattern of serological reactivity which did not correspond to any of the known leukocyte differentiation antigen clusters. We describe here the cloning and sequencing of a cDNA encoding the CMRF35 antigen by means of expression in COS cells and immunoselection with the CMRF35 monoclonal antibody. The cDNA encodes a novel integral membrane glycoprotein of 224 amino acids that represents a new member of the immunoglobulin (Ig) gene superfamily. The molecule comprises (a) a single extracellular Ig variable domain remarkably similar to the Fc receptor for polymeric IgA and IgM, (b) a membrane‐proximal domain containing a high proportion of proline, serine and threonine residues that was predicted to be heavily O‐glycosylated, (c) an unusual transmembrane anchor that contained a glutamic acid and a proline residue and (d) a short cytoplasmic tail. Transcripts encoding the CMRF35 protein were detected in early monocytic cell lines, in peripheral blood T cells and in some B lymphoblastoid cell lines, confirming the results of immunocytological staining. However, the level of CMRF35 expression on peripheral blood T cells was shown to decrease in response to mitogenic stimulation. The likelihood that the CMRF35 antigen shares a common evolutionary ancestor with the poly Ig Fc receptor is discussed.
An alternative pathway of B cell activation: stilbene disulfonates interact with a Cl− binding motif on AEn‐related proteins to stimulate mitogenesis
Authors: Deane Katherine H. O. , Mannie Mark D. 
Published: March 2007

AbstractStilbene disulfonates are known to competitively inhibit Cl−/HCO3− flux through Band 3‐related anion exchange (AE) proteins. To study the role of AE in lymphocyte activation, stilbene disulfonates were added to cultures of rat splenocytes (SPL). Four different stilbene derivatives were tested and each directly stimulated mitogenic proliferative responses of SPL. The mitogenic activity of these analogs paralleled their known patterns of interaction with Band 3‐related AE proteins, as measured by; (a) their effective mitogenic concentrations, (b) their rank order of mitogenic potency [DIDS > SITS > DNDS ⋍ DAzDS], (c) their patterns of nonreversible binding to the mitogenic receptor [DIDS ≫ SITS, DNDS], and (d) the specific, noncompetitive inhibition of their activity by the antagonist niflumic acid. Stilbene disulfonates directly activated purified B cell populations but not isolated T cells and furthermore, acted in synergy with anti‐IgM to stimulate proliferation of SPL. These findings show that stilbene disulfonates represent a novel class of mitogens that interact with AEn‐related proteins to stimulate an alternative activation pathway in B cells. These studies also indicate that immunomodulating activities of nonsteroidal anti‐inflammatory drugs such as niflumic acid may by mediated, in part, by their interactions with AEn‐related proteins.
High‐level expression of a human immunoglobulin γ1 transgene depends on switch region sequences
Authors: Gram Hermann , Zenke Gerhard , Geisse Sabine , Kleuser Beate , Bürki Kurt 
Published: March 2007

AbstractWe describe that chimeric mouse‐human immunoglobulin heavy chain (IgH) genes lacking a switch region and controlled by an IgH promoter and the intronic enhancer are only weakly expressed in transgenic mice. Insertion of part of the human Cγ1 or murine Cμ switch region into the major intron of the chimeric IgH gene results in a 102‐to 103‐fold increase in transgene expression. Analysis of B cell hybridoma clones from transgenic mice suggests that switch sequences influence IgH transgene expression at the cellular level. However, the effect of switch region sequences on IgH gene expression observed in vivo is not apparent in transfected B cell lines. These results indicate that switch region sequences which are located proximal to the constant part of the gene and which are normally present in a rearranged IgH gene after class switching represent a novel type of regulatory element that plays a critical role in IgH gene expression in vivo.
Immune regulation in self tolerance: functional elimination of a self‐reactive, counterregulatory CD8+ T lymphocyte circuit by neonatal transfer of encephalitogenic CD4+ T cells lines
Authors: Qin Yufen , Sun Deming , Wekerle Hartmut 
Published: March 2007

AbstractTransfer of encephalitogenic, CD4+ T lymphocyte lines into syngeneic adult Lewis rats not only leads to the development of experimental autoimmune encephalomyelitis (EAE), but, in addition, to the expansion of counterregulatory, CD8+ T lymphocyte clones which are able to lyse specifically the encephalitogenic T cells in vitro and to neutralize their encephalitogenic capacity in vivo. In striking contrast, in neonatal rats, which still lack myelin (autoantigens), injection of the same encephalitogenic lines neither mediates EAE, nor confers protection in later life against the myelin‐specific T cells. In fact, this treatment results in the life‐long functional elimination of counterregulatory, clonotypic CD8+ T lympholcytes, which cannot even be reinduced by repeated injections of the relevant CD4+ T line. These data seem to point to a self‐protective T cell control mechanism which is developed within the immune system prior to, and thus independent of the appearance of the appropriate self antigen.
Expression and function of the neural cell adhesion molecule L1 in mouse leukocytes
Authors: Kowitz Aiga , Kadmon Guni , Eckert Marion , Schirrmacher Volker , Schachner Melitta , Altevogt Peter 
Published: March 2007

AbstractThe neural cell adhesion molecule L1 is a cell surface glycoprotein of the immunoglobulin superfamily which mediates adhesion between neural cells. The possibility that similar cell‐cell recognition mechanisms may be shared by the nervous and immune systems prompted us to study the expression and function of L1 in cells of the hematopoietic system. Immunofluorescence analysis using monoclonal L1 antibody revealed that the molecule is expressed in the bone marrow, spleen, and thymus of the mouse. This observation was confirmed by amplifying cDNA derived from these organs by the polymerase chain reaction with L1‐specific oligonucleotide primers. Two‐color fluorescence analysis indicated that bone marrow lymphoid and granulocyte precursor cells express low and high levels of L1, respectively. In the thymus L1 is primarily expressed by mature cells that have a strong expression of CD3 and in the spleen both B cells and T cells express L1.The possible function of L1 in lymphoid cells was studied using subcloned ESb‐MP lymphoma cells having high or low densities of L1 on the cell surface as well as activated splenic B lymphoblasts. Parental and subcloned ESb‐MP cells that strongly expressed L1 could form homotypic aggregates in the presence of low Ca2+ levels, whereas subcloned ESb‐MP cells with a weak expression of L1 did not aggregate, suggesting that L1 mediates the Ca2+‐independent aggregation of the parental ESb‐MP cells. Furthermore, the aggregation of activated B lymphoblasts under physiological concentrations of Ca2+ and Mg2+ was inhibited by 30% in the presence of Fab fragments of polyclonal L1 antibodies, implying that L1 also mediates adhesion among normal lymphoid cells. A possible role of L1 on lymphocytes in stimulating the innervation of lymphoid organs is discussed.
Inhibitory and stimulatory signaling via immunoglobulin receptors: dichotomous responses elicited in clonal B cell populations
Authors: Van Endert Peter M. , Moldenhauer Gerhard 
Published: March 2007

AbstractThe paradox that cross‐linking of IgM antigen receptors on B cells by native or surrogate antigen can inhibit, as well as stimulate, B cell functions has previously been attributed to changes during maturation and activation, programming either a negative or a positive response at defined developmental stages. In contrast to this concept, we show here that some B cells possess the potential for both types of response at the same stage. In three clonal malignant human B cell populations, bivalent soluble monoclonal antibodies to IgM or idiotype, but not IgD completely inhibited spontaneous DNA synthesis, but significantly induced [3H]thymidine uptake when coupled to insoluble compounds. In co‐incubation experiments mitogenic stimuli were dominant over inhibitory ones and were still effective after prolonged pretreatment of the B cells with inhibitory reagents. Ionomycin, known to increase intracellular calcium levels, and low doses of phorbol ester, described to activate protein kinase C, also suppressed DNA synthesis. High doses of phorbol ester alone or in combination with ionomycin, however, induced DNA synthesis in two of the lymphomas. We conclude that some B cells may respond to cross‐linking of surface IgM in a dose‐dependent manner so that all signals increase DNA synthesis once a threshold has been reached. These dose‐dependent effects may in part involve signaling via breakdown of membrane inositol phosphates.
Tumor necrosis factor‐α production induced in T lymphocytes through the AIM/CD69 activation pathway
Authors: Santis Ana G. , Campanero Miguel R. , Alonso Jose L. , Tugores Antonio , Alonso Miguel A. , Yagüe Enriqueta , Pivel Juan P. , Sánchez‐Madrid Francisco 
Published: March 2007

AbstractHuman activation inducer molecule (AIM/CD69), a dimeric glycoprotein of 33 and 27 kDa, is the earliest inducible cell surface antigen expressed during lymphocyte activation, which has been also involved in lymphocyte proliferation. Although AIM is absent from peripheral blood resting lymphocytes, it is expressed by in vivo activated lymphocytes infiltrating sites of chronic inflammation in several pathologies, as well as by lymphocytes after in vitro activation with different stimuli. We have investigated the possibility that tumor necrosis factor‐α (TNF‐α) gene expression and protein secretion could be induced in peripheral blood T cells through the AIM/CD69 molecule. Anti‐AIM monoclonal antibodies (mAb) were able to induce TNF‐α secretion in T cells when protein kinase C (PKC) was simultaneously activated by treatment with phorbol esters. TNF‐α secretion was detected at 24 h and peaked at day 3 upon T lymphocyte activation with anti‐AIM mAb. Immunoprecipitation studies with an anti‐TNF‐α mAb from surface iodinated T cells activated through AIM, demonstrated that TNF‐α first appeared as a cell surface molecular form of 26 kDa, which is subsequently released to the extracellular medium as the 17‐kDa molecular form of TNF‐α. AIM stimulation dramatically increased TNF‐α mRNA levels, and this mRNA induction and subsequent TNF‐α secretion were virtually abrogated by the immunosuppressive drug cyclosporin A. Taken together these results indicate that AIM constitutes a novel molecular pathway in T lymphocytes for induction of TNF‐α, and suggest a relevant pathologic role for AIM+ lymphocytes located at sites of tissue injury in the pathogenesis of different chronic inflammatory diseases.
Capacity of antigen uptake by B cells, fibroblasts or macrophages determines efficiency of presentation of a soluble self antigen (C5) to T lymphocytes
Authors: Stockinger Brigitta 
Published: March 2007

AbstractSelf antigens in the body fluids must be taken up, processed and presented by antigen‐presenting cells (APC) in order to induce T cell tolerance. For self antigens like the fifth component of complement (C5) which is not picked up by APC via antigen‐specific receptors, presentation has to rely on uptake by nonspecific means. C5 was used as a model soluble self antigen to study the capacity of different APC (B lymphoma cells, fibroblasts and macrophages) of taking up, processing and presenting low concentrations of soluble C5 to C5 specific T cell hybrids. Under conditions of limiting antigen amounts macrophages and fibroblasts exhibited similar presentation capacity for soluble C5 while B cells did not. C5 presentation by macrophages was enhanced in the presence of C5‐specific antibody and augmented further if antigen was added in the form of particulate latex‐antigen‐antibody complexes indicating enhanced uptake via Fc receptor‐mediated endocytosis or phagocytosis. B cells presented soluble C5 only in the presence of C5‐specific antibody. Uptake of C5 under these conditions occurred via Fc receptors type II. This pathway of antigen uptake did not operate with other antigens which were presented efficiently after nonspecific endocytosis.In light of these findings it seems reasonable to propose that nonspecific endocytosis of serum proteins like C5 by B cells is normally limited in order to avoid interference with their critical role in antigen receptor‐mediated uptake and presentation for the initiation of an antibody response. It seems likely that presentation of soluble self antigens present in the circulation may normally be the task of dendritic cells and macrophages depending on the physical shape of the antigen.