bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipopolysaccharide induces human interleukin‐1 receptor antagonist and interleukin‐1 production in the same cell
Authors: Andersson Jan , Björk Lars , Dinarello Charles A. , Towbin Harry , Andersson Ulf 
Published: March 2007

AbstractA new member of the interleukin‐1 (IL‐1) family has recently been described. Human IL‐1 receptor antagonist (IL‐1ra) is structurally related to IL‐1α and IL‐1β but binds to IL‐1 receptors on various target cells without demonstrable agonist activity. Understanding the mechanisms of regulation of IL‐1ra production may clarify the biology of this unique cytokine as well as elucidate its possible role as a natural anti‐inflammatory protein. The effects of lipopolysaccharide (LPS) on IL‐1α, IL‐1β and IL‐1ra production was studied at a single‐cell level by use of cytokine‐specific antibodies and indirect immunofluorescence technique. The peak synthesis of IL‐1ra and IL‐1α/β occurred in peripheral blood monocytes obtained from healthy blood donors within 4 and 6 h of cell stimulation, respectively. By double‐staining procedure all IL‐1ra‐positive cells were also IL‐1α and/or β positive. Thus, endotoxin induced simultaneous synthesis of the IL‐1 gene family in the same cells. Only monocytes contributed to the production of IL‐1α, β and IL‐1ra during the 96 h of cell culture. The maximum number of IL‐1ra‐producing monocytes was 48 ± 16% as compared to peak production of IL‐1α and β which occurred in 75 ± 9% and 80 ± 12% (p < 0.001), respectively, of all peripheral blood monocytes. The incidence of IL‐1α and β‐containing cells was not only significantly higher but also occurred for a longer time period, 72 h as compared to 24 h for IL‐1ra localized in the Golgi organelle. However, IL‐1ra‐containing cells with a diffuse cytoplasmic appearance were also evident (20%–30%) at a later stage, 12 to 72 h after stimulation. Blocking IL‐1 surface receptors by addition of exogenous recombinant IL‐1β before stimulation could not inhibit the diffuse cytosolic localization. This indicates that the „late”︁ staining pattern did not reflect IL‐1ra being secreted and internalized after binding to extracellular receptors. Thus, perhaps IL‐1ra modulates IL‐1 effector mechanisms by receptor interactions both inside and outside the cell.
T cell repertoire in tuberculosis: selective anergy to an immunodominant epitope of the 38‐kDa antigen in patients with active disease
Authors: Vordermeier Hans‐M. , Harris David P. , Friscia Giuseppe , Román Eulogia , Surcel Heljä‐Marja , Moreno Carlos , Pasvol Geoffrey , Ivanyi Juraj 
Published: March 2007

AbstractIt is generally accepted that both host protection and pathogenic reactions in tuberculosis are mediated by T lymphocytes. However, little is known about the structures and discreet functions of epitopes stimulating the immune response. In this study, proliferative responses of blood T lymphocytes to synthetic peptides derived from the sequence of the 38‐kDa antigen from Mycobacterium tuberculosis have been investigated in 41 healthy individuals and in 36 patients with active tuberculosis. Of the healthy purified protein derivative (PPD)‐positive donors, 90% responded to a permissively recognized peptide, 38.G (residues 350–359), located at the carboxy terminus of the molecule. Four other permissively recognized epitopes of this molecule (38.A, 38.I, 38.E, 38.K) were stimulatory for more then 50% of healthy PPD‐positive individuals. Patients with lymphatic tuberculosis responded to these peptides in a similar manner. In contrast, we observed a selective anergy to stimulation with peptide 38.G in the majority of patients with pulmonary (11% responders) and nonlymphatic extrapulmonary tuberculosis (25% responders). The lack of responsiveness to 38.G was epitope specific since the degree of responsiveness to the other four permissively recognized peptide epitopes was similar for patients and PPD‐positive controls. Using the PEPSCAN technology and truncated peptides, the core epitope of 38.G was localized to a peptide 10 amino acids long (HFQPLPPAVV). This minimal structure was capable of inducing a proliferative response in all healthy 38.G responders tested. The mechanisms influencing this epitope‐specific anergy in patients could give new insights into the immunopathogenesis of tuberculosis.
Expression of major histocompatibility complex class I antigens at low levels in the thymus induces T cell tolerance via a non‐deletional mechanism
Authors: Husbands Sandra D. , Schönrich Gunther , Arnold Bernd , Chandler Phillip R. , Simpson Elizabeth , Philpott Karen L. , Tomlinson Peter , O'Reilly Lorraine , Cooke Anne , Mellor Andrew L. 
Published: March 2007

AbstractTransgenic CBA (H‐2k haplotype) mice expressing the H‐2 Kb major histocompatibility complex (MHC) class I gene under control of transcriptional promoter elements from a milk protein gene display high‐level H‐2 Kb transcription in lactating mammary glands and low‐level transcription in skin and thymus of male and virgin female transgenic mice. However, H‐2 Kb antigen could be detected only in lactating mammary gland epithelial cells by immunohistological methods. All transgenic mice are tolerant of H‐2 Kb since they fail to reject skin grafts from mice expressing H‐2 Kb molecules. Furthermore, anti‐H‐2 Kb cytotoxic responses could not be generated using responder T cells from transgenic mice but T cells from the same mice proliferated, in the presence of interleukin‐2, in response to stimulator cells expressing H‐2 Kb. Tolerance to H‐2 Kb is induced in the thymus since CBA mice grafted with thymus tissue from transgenic mice fail to reject H‐2 Kb disparate skin grafts. However, experiments with double‐transgenic mice also expressing a T cell receptor with anti‐H‐2 Kb specificity reveal that tolerance induction is not brought about by elimination of thymocytes bearing H‐2 Kb‐reactive receptors. Instead, a non‐deletional mechanism which results in down‐modulation of both CD8 and T cell receptor expression in peripheral T cells correlates with the induction of tolerance in these mice. These data reveal that extremely low levels of self‐antigen expression in the thymus are sufficient to induce tolerance via non‐deletional mechanisms.
Paroxysmal nocturnal hemoglobinuria due to hereditary nucleotide deletion in the HRF20 (CD59) gene
Authors: Motoyama Noboru , Okada Noriko , Yamashina Manabu , Okada Hidechika 
Published: March 2007

AbstractHRF20 (CD59) is a membrane glycoprotein which protects cells from the membrane attack reaction of homologous complement. A patient who is completely deficient in HRF20 expression and is suffering from paroxysmal nocturnal hemoglobinuria (PNH) was studied. His parents are cousins and both have decreased HRF20 expression, suggesting that the deficiency is genetic. We established a cultured cell line (NCU1) which is HRF20 deficient from the patient's lymphocytes by Epstein‐Barr‐virus (EBV) infection. Northern blot analysis revealed HRF20 mRNA signals, indicating that HRF20 mRNA were transcribed. HRF20 cDNA was amplified by the polymerase chain reaction (PCR) method. Sequencing of the cDNA from the NCU1 showed two single‐base deletions at amino acid 16 and 96 from the N terminus of the mature protein. Deletion in the genomic DNA of peripheral blood lymphocytes was confirmed by the DNA sequence of an HRF20 open reading frame containing amino acid 16. Furthermore, the patient's parents and sister possessed both intact and deleted genomic HRF20 DNA while his brother's DNA was intact. These findings demonstrate that the HRF20 deficiency was genomic in origin, and that complete deletion was brought about by a homozygous abnormality in the HRF20 gene. The base deletion caused a codon frame shift resulting in failure to produce intact HRF20 protein in the patient.
α1‐Acid glycoprotein potentiates lipopolysaccharide‐induced secretion of interleukin‐1 β, interleukin‐6 and tumor necrosis factor‐α by human monocytes and alveolar and peritoneal macrophages
Authors: Boutten Anne , Dehoux Monique , Deschenes Marianne , Rouzeau Jean‐Denis , Bories Phuong Nhi , Durand Geneviève 
Published: March 2007

AbstractAlthough the physiological role of α1‐acid glycoprotein (AGP), an acute‐phase protein, is poorly understood, several lines of evidence support a modulatory action on the immune response. In this study, we investigated the effect of AGP on the production of interleukin (IL)‐1β, IL‐6 and tumor necrosis factor (TNF)‐α by human monocytes, macrophages and the monocytic THP‐1 cell line. AGP significantly enhanced (2‐ to 7‐fold) the production of these cytokines in monocytes induced by suboptimal concentrations of lipopolysaccharide [E. coli lipopolysaccharide (LPS): 100 ng/ml] in serum‐free conditions, whereas it had little or no effect in the absence of LPS. The potentiating effect of AGP was inhibited by specific antibodies. It was concentration dependent and the greatest enhancement was observed with 250–500 μg/ml. Moreover, AGP only potentiated the effect of suboptimal concentrations of LPS. AGP did not alter the time course of LPS‐induced IL‐1β, IL‐6 or TNF‐α secretion. AGP acts as a co‐inducer and could also potentiate cytokine secretion triggered by Neisseria meningitidis LPS and muramyl dipeptide. The glycan moiety of AGP did not seem to be involved in its potentiating effect, since both its major glycoforms and asialo‐AGP potentiated the effect of LPS to the same extent as native AGP. Possible differences in the effect of AGP according to cell maturation were investigated using isolated human macrophages: AGP potentiated LPS‐induced cytokine production by both peritoneal and alveolar macrophages. These data suggest that AGP can modulate monocyte/macrophage functions, thereby contributing to the amplification and regulation of immune and inflammatory responses.
Assessment of major histocompatibility complex class I interaction with Epstein‐Barr virus and human immunodeficiency virus peptides by elevation of membrane H‐2 and HLA in peptide loading‐deficient cells
Authors: Stuber György , Modrow Susanne , Höglund Petter , Franksson Lars , Elvin John , Wolf Hans , Kärre Klas , Klein George 
Published: March 2007

AbstractEarlier findings indicate that peptides can affect the expression of major histocompatibility complex (MHC) class I molecules on the surface of cells with defective peptide loading mechanism. We have used peptide induced increase of class I antigen expression to assess peptide interaction with MHC class I molecules. A panel of 41 overlapping synthetic peptides derived from the human immunodeficiency virus‐1 (HIV‐1) gag protein and 33 nonoverlapping peptides from Epstein‐Barr virus (EBV) proteins EBNA‐1, 2, 3, 4, 5, 6, LMP, BZLF2, BILF2, BSLF2, BALF4 and BcLF1 was assessed for the ability to enhance the expression of HLA‐A2.1, H‐2Db, Kb and Dd on the murine RMA‐S and human 721.174/T2 (.174/T2) lines by indirect immunofluorescence. Considering doubling of the fluorescence intensity in the peptide‐treated samples as positivity, 6 of 39 HIV and 1 of 32 EBV peptides were found to bind to A2.1, 6 of 39 HIV gag and 7 of 16 EBV peptides to Db, 8 of 39 HIV gag and 5 of 16 EBV peptides to Kb and 2 of 39 HIV gag and 1 of 17 EBV peptides to Dd. The sensitivity of the method is comparable to the in vitro class I assembly assay with conformation‐dependent monoclonal antibody and is more discriminating than the solid‐phase assay. Due to its simplicity this method can also serve for testing large peptide panels for binding capacity to various class I molecules. Moreover, the method provides information about the relevance of in vitro tests for class I assembly in living cells.
Self tolerance to human A and B histo‐blood group antigens exists at the B cell level and cannot be broken by potent polyclonal B cell activation in vitro
Authors: Rieben Robert , Tucci Alessandra , Nydegger Urs E. , Zubler Rudolf H. 
Published: March 2007

AbstractIt is generally considered that tolerance to self antigens is less complete in B than in T lymphocytes. However, B cell tolerance through either functional inactivation (anergy) or clonal deletion has been demonstrated in transgenic mice. In the present study, we investigated whether B cells specific for self A/B histo‐blood group antigens can be detected in normal humans. It is a key feature of the ABO system that all normal individuals make natural antibodies against those A or B carbohydrates which are not present in their organism. To detect B cells by the limiting dilution approach we used a specific enzyme‐linked immunosorbent assay for the quantitation of anti‐A/B antibodies, and a culture system in which polyclonal B cell activation occurs through cell contact with EL4 thymoma cells. As was reported for other B cell studies, we frequently detected „polyreactive”︁ immunoglobulin (Ig)M (but not IgG) with apparent autoreactivity but of uncertain significance regarding physiologic conditions. However, A‐ or B‐specific B cell responses occurred with selective patterns in agreement with classical blood group serology in 14 individuals with A, B, AB or 0 blood group phenotypes: 1/11 600 B cells made anti‐allo A/B IgM and 1/26 500 B cells such as IgG, while only 1/104 000 B cells apparently made anti‐self A/B IgM and 1/350 000 B cells such as IgG. This shows self tolerance at the B cell level. Since anergy of B cells can frequently be broken by polyclonal B cell activation in vitro, and EL4 cells are potent B cell stimulators, the present results argue for either a highly resistant anergic state or for clonal deletion of self‐A/B histo‐bloos group‐specific human B cells.
A versatile method to produce antibodies to human T cell receptor Vβ segments: frequency determination of human Vβ2+ T cells that react with toxic‐shock syndrome toxin‐1
Authors: Romagné François , Besnardeau Lydia , Malissen Bernard 
Published: March 2007

AbstractHuman Vβ (hVβ) regions have been expressed in the context of mouse T cell receptor (TcR)‐CD3 complexes, and subsequently used to raise hVβ‐specific monoclonal antibodies (mAb). The method of expression of hVβ outlined in this report contrasts in its versatility with the one reported by Choi et al. (Proc. Natl. Acad. Sci. USA 1991. 88: 8357). For instance, we have applied it successfully to the construction of mouse T cell transfectants expressing hVβ1, hVβ2, hVβ3, hVβ8, hVβ9, hVβ13.5, hVβ19, hVβ21, and hVβ22 gene segments. mAb against the hVβ2 and hVβ19 regions have been raised by using these transfectants as immunogens in mice. Here, we illustrate the application of the anti‐hVβ mAb to the measurement of human T cells that react with the staphylococcal toxic‐shock syndrome toxin‐1.
The B29 and mb‐1 polypeptides are differentially expressed during human B cell differentiation
Authors: Mason David Y. , Van Noesel Carel J. M. , Cordell Jacqueline L. , Marieke Comans‐Bitter W. , Micklem Kingsley , Tse Albert G. D. , Van Lier René A. W. , Van Dongen4 Jacques J. M. 
Published: March 2007

AbstractSurface immunoglobulin on mouse B cells is associated with a heterodimer comprising the products of the mb‐1 and B29 genes. Here we report that antibodies raised against a peptide sequence from the intracytoplasmic C terminus of the B29 murine gene product detect the 37‐kDa component of the human heterodimer, indicating that this component in man is also encoded by the B29 gene. The immunocytochemical reactivity of these anti‐B29 antibodies was compared with those of antibodies to the mb‐1 protein. Of 25 cases of acute lymphoblastic leukaemia (ALL), 24 were positive for mb‐1 whereas B29 was expressed in only 13 cases. Most of these B29‐positive ALL expressed immunoglobulin μ heavy chain in their cytoplasm (pre‐B ALL). In lymphoid tissue sections, anti‐B29‐labeled B cell follicles in a similar fashion to anti‐mb‐1, with the striking exception that plasma cells were unreactive for B29, but positive for mb‐1. These results suggest that the synthesis of B29 begins later in precursor B cells than that of mb‐1, and ceases before the terminal plasmacyte phase.
Differentiation‐specific expression of a novel G protein‐coupled receptor from Burkitt's lymphoma
Authors: Dobner Thomas , Wolf Ingrid , Emrich Thomas , Lipp Martin 
Published: March 2007

AbstractDeregulation of the proto‐oncogene MYC by specific chromosomal translocations has been shown to be essential but not sufficient for the development of Burkitt's lymphoma (BL). To identify other genes which either mark important steps in tumorigenesis or which reflect the cellular differentiation state of BL cells we have compared tumor cells to immortalized lymphoblastoid B cells by subtractive hybridization. We have identified a complementary DNA clone which encodes a novel member of the superfamily of GTP‐binding (G) protein‐coupled receptors, designated BLR1. The corresponding mRNA is expressed in BL and lymphatic tissues but not in other cell lines either of the B cell lineage or of other hematopoietic or non‐hematopoietic origin. This exclusive expression of BLR1 and the oncogenic potential of this receptor class supports the hypothesis that BLR1 exerts a regulatory function in BL lymphomagenesis and/or B cell differentiation. Moreover, the protein sequence is highly related to that of receptors for the cytokine interleukin (IL)‐8 and other neutrophil chemoattractants. We conclude that BLR1 may represent a potential candidate involved in the process of physiologic trafficking, cell‐cell interactions, and activation of mature B lymphocytes in lymphatic tissues.
Proliferation and differentiation of human CD5+ and CD5− B cell subsets activated through their antigen receptors or CD40 antigens
Authors: Defrance Thierry , Vanbervliet Béatrice , Durand Isabelle , Briolay Jérǒme , Banchereau Jacques 
Published: March 2007

AbstractThe pan‐T cell antigen CD5 has been shown to delineate two different mouse B cell subsets, originating from distinct progenitors. In man, on average, 30% of the tonsillar B cell pool expresses this antigen. In the present report, a detailed comparison of the CD5+ and CD5− B cell response to cytokines, following activation via surface immunoglobulins (sIg) or CD40 antigen, was undertaken. CD5+ B cells were positively selected by panning or by sorting from tonsils. Two‐color immunofluorescence analysis performed on tonsillar B cell populations showed that CD5+ B cells displayed most of the phenotypic features of mantle zone B cells. CD5+ B cells could be stimulated for DNA synthesis by mitogenic concentrations of Staphylococcus aureus, Cowan I strain (SAC), insolubilized anti‐IgM antibodies, immobilized anti‐CD40 antibodies and phorbol 12‐myristate 13‐acetate (PMA). The growth‐response of small dense CD5− B cells to these T cell‐independent mitogens was comparable to that of CD5+ B cells, whereas the low‐density, in vivo‐activated, CD5− B cells were only marginally stimulated by Ig‐cross‐linking agents and PMA. Following ligation of sIg, both B cell subsets proliferated essentially in response to interleukin (IL)‐2 and IL‐4. When used in co‐stimulation with immobilized anti‐CD40 antibodies, IL‐4 promoted growth of CD5+ and CD5− B cells, whereas IL‐2 displayed only moderate stimulatory effects. CD5+ and CD5− B cells differentiated into Ig‐secreting cells when they were co‐cultured with SAC or cross‐linked anti‐CD40 antibodies and IL‐2. However, IgM constituted the major component of the Ig response of CD5+ B cells, whereas high levels of IgG were secreted by CD5− B cells.
Expression and biological activity of interleukin‐1 receptors in mouse γ/δ thymocytes during ontogeny
Authors: Liberman Isabelle , Sarthou Pierre , Cazenave Pierre‐André , Rueff‐Juy Dominique 
Published: March 2007

AbstractWe have recently shown that the response of mouse thymocytes to interleukin (IL)‐1 + IL‐2 was maximal at birth and that the responding cells displayed a CD4−CD8− T cell receptor (TcR) γ/δ+ phenotype. Unexpectedly, despite their high proportion of γ/δ+ cells, fetal thymocyte populations responded only weakly to IL‐1 + IL‐2. In this report, we demonstrate that the discrepancy between the day 17.5 fetal and newborn sensitivities to the combined action of IL‐1 and IL‐2 is a consequence of the different patterns of high‐affinity IL‐1 receptor (IL‐1R) expression displayed by these two cell subsets. Actually, high‐ and low‐affinity IL‐1R are found in TcR γ/δ+ newborn cells and, in contrast, only low‐affinity IL‐1R are detectable in day 17.5 fetal cells. Our binding and functional studies strongly support the hypothesis that high‐affinity IL‐1R on the one hand, and low‐affinity ones on the other hand, are involved in the response to IL‐1 + IL‐2 of newborn and day 17.5 fetal thymocytes, respectively. In addition, the high‐affinity IL‐1R appear to be far more efficient than the low‐affinity receptors in promoting IL‐2 responsiveness of thymocytes.
Integrins and other adhesion molecules on lymphocytes from synovial fluid and peripheral blood of rheumatoid arthritis patients
Authors: Takahashi Hiroki , Söderström Kalle , Nilsson Ethel , Kiessling Rolf , Patarroyo Manuel 
Published: March 2007

AbstractCell and matrix adhesion of lymphocytes participates in homing, migration and accumulation of these cells in inflamed tissues as well as in the generation of immune and inflammatory responses. In inflamed joints of rheumatoid arthritis (RA) patients, lymphocytes accumulate in the synovial membrane and the synovial fluid. In the present study we have analyzed the expression of integrins and other adhesion molecules in synovial fluid lymphocytes (RA‐SFL) and paired peripheral blood lymphocytes (RA‐PBL) from 21 RA patients by immunofluorescence flow cytometry. We have also investigated the expression of these adhesion molecules on peripheral blood lymphocytes obtained from 13 sex‐ and age‐matched healthy controls (CO‐PBL). RA‐SFL, which consisted mostly of T cells, showed higher expression of the integrin subunits β1 (CD29), VLA‐1α, −3α, −4α, −5α and −6α when compared to RA‐PBL. In turn, RA‐PBL showed lower expression of these molecules than CO‐PBL. The expression of the immunoglobulin‐related molecules CD2, CD54 (ICAM‐1) and CD58 (LFA‐3) was higher on RA‐SFL when compared to RA‐PBL or CO‐PBL, and similar results were obtained with the β2 integrin subunits CD11a and CD18. In contrast, L‐selectin (LECAM‐1) and ICAM‐2 were expressed at much lower levels on RA‐SFL than on RA‐PBL or CO‐PBL. CD44, a receptor for hyaluronic acid and collagen, was expressed by most RA‐SFL, RA‐PBL and CO‐PBL cells but at higher density on RA‐SFL. The results indicate that RA‐SFL express a distinct array of adhesion molecules, similar to the one of memory T lymphocytes. This characteristic phenotype may contribute to the lymphocytic infiltration of the synovium and to the pathogenesis of RA.