bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin-12 can replace CD28-dependent T-cell costimulation during nonspecific cytotoxic T lymphocyte induction by anti-CD3 antibody
Authors: Makrigiannis Andrew P , Musgrave Bruce L , Haeryfar S M Mansour , Hoskin David W 
Published: September 2022

AbstractCytotoxic T lymphocyte (CTL) development is regulated closely by an intricate series of signals provided by the T-cell receptor/CD3 complex, cytokines, and costimulatory ligand/receptor systems. In this study, we have explored the role of interleukin (IL)-12 and CD28 in mouse CTL development. Activation of T cells with anti-CD3 monoclonal antibody (mAb) in the presence of anti-CD86 mAb, which prevents CD28-CD86 interaction, led to decreased production of type 1 (IL-2, interferon-γ) and type 2 (IL-4, IL-6, IL-10) cytokines, as well as diminished expression of granzyme B (Gzm B) and reduced cytotoxic effector function. Cytolytic activity in T-cell cultures that were activated in the presence of anti-CD86-blocking mAb alone or in combination with anti-CD80 mAb could be restored by the addition of exogenous IL-12 at initiation of culture. The ability of IL-12 to substitute for CD28-costimulatory signaling during CTL development was found to be dependent on the presence of IL-2 rather than interferon-γ. IL-2 is required for IL-12Rβ2 expression by T cells activated in the presence of anti-CD86 mAb. Moreover, IL-12Rβ2 expression by T cells activated in the presence of anti-CD86 mAb is enhanced by IL-12. We, therefore, conclude that the ability of IL-12 to substitute for CD28-costimulatory signaling during CTL development is a result of the interaction of IL-12 with IL-12Rβ2 induced by low levels of IL-2 synthesized by T cells activated in a CD28-independent manner.
Role of mast cells in zymosan-induced peritoneal inflammation in Balb/c and mast cell-deficient WBB6F1 mice
Authors: Kolaczkowska Elzbieta , Seljelid Rolf , Plytycz Barbara 
Published: September 2022

AbstractZymosan-induced peritonitis was investigated in mast cell-deficient WBB6F1 mice and in Balb/c mice pretreated with mast cell stabilizer (cromolyn) or antagonists of histamine receptors (mepyramine, triprolidine, cimetidine, or ranitidine). The inherited mast cell deficiency in W/Wv knockouts of WBB6F1 mice impaired significantly the level of histamine and plasma exudation (measured 30 min after stimulation) as well as the influx of exudatory leukocytes, accumulation of plasma and exudate chemoattractants, and the release of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) measured at 6 h of inflammation. All of those factors were fully restored after selective intraperitoneal reconstitution of W/Wv mice with bone marrow-derived mast cells from their control +/+ counterparts. Cromolyn pretreatment of Balb/c mice reduced exclusively the early plasma exudation and histamine influx. Blocking of histamine receptors inhibited not only the early plasma exudation but also temporarily diminished primary leukocyte influx and levels of MCP-1 and IL-1β. In conclusion, mast cells play an important role in the initiation of zymosan-induced peritonitis and modulate its further course.
Neutrophil secretory vesicles are the intracellular reservoir for GPI-80, a protein with adhesion-regulating potential
Authors: Dahlgren Claes , Karlsson Anna , Sendo Fujiro 
Published: September 2022

AbstractThe subcellular localization of GPI-80, a novel, adhesion-regulating protein, was investigated in human neutrophils. Surface expression of GPI-80 was determined by FACS analysis as well as by the ability for phospholipase C to cleave the protein from the cell surface. Increasing amounts of GPI-80 were exposed on the cell surface after weak stimulation with the chemoattractant fMLF, suggesting that the protein can be translocated to the plasma membrane from intracellular stores. By subcellular fractionation of the neutrophils, GPI-80 was defined as a component of a light membrane fraction, containing secretory vesicles and plasma membranes, and it was absent from the neutrophil granule fractions. Separation of the plasma membranes from the secretory vesicles by flotation gradient fractionation confirmed that the GPI-80 was localized in the mobilizable secretory vesicles by approximately 50%, and the rest was plasma membrane-bound. Thus, we identify secretory vesicles as the reservoir of GPI-80 from which it may translocate to the plasma membrane after weak stimulation of the cells.
Chronic granulomatous disease: more than the lack of superoxide?
Authors: Geiszt Miklós , Kapus András , Ligeti Erzsébet 
Published: September 2022

AbstractChronic granulomatous disease (CGD) is an inherited disease characterized by severe and recurrent bacterial and fungal infections manifested in most cases in early childhood. Phagocytic cells of CGD patients are unable to produce superoxide anions, and their efficiency in bacterial killing is significantly impaired. Recent work has shown alterations in the electrophysiological properties of CGD granulocytes, which might contribute to the pathogenesis of the disease. The new aspects that we discuss in this review concern the proton channel function of gp91phox (the electron-transporting subunit of the NADPH oxidase) and the electrogenic activity of the active enzyme complex, which can affect the transmembrane trafficking of several ions. Based on the reviewed data, we also propose a hypothesis that the absence of a functional NADPH oxidase in CGD neutrophils could result in altered ion compositions within intracellular and intraphagosomal spaces during the process of phagocytosis.
Activation-induced expression of CD1d antigen on mature T cells
Authors: del C. Salamone María , Rabinovich Gabriel A , Mendiguren Ana K , Salamone Gabriela V , Fainboim Leonardo 
Published: September 2022

AbstractIn the present study, we investigated the expression of human CD1d antigen on activated mature T cells. Expression of this glycoprotein was found to be highly regulated and dependent on PHA stimulation. Flow cytometry studies using the NOR3.2 antibody, which recognized CD1d under denaturing conditions, showed a clear increase in its expression after PHA stimulation. Expression of this molecule after PHA activation was confirmed by analysis of its corresponding transcript by RT-PCR. A single band representing mRNA for CD1d membrane isoform was observed in activated PBMC as well as in ER3 CD1D-transfected and MOLT-4, pre-T cell lines, which were used as controls. Western blot analysis revealed an activation-dependent increase in CD1d protein expression when PBMC and enriched T cells were activated for different time periods. Activation-dependent expression of CD1d antigen was also confirmed in allogenic-activated T cells, suggesting that this event could have biological significance. Finally, immunocytochemical studies showed the presence of this protein at the plasma membrane accompanied by a cytoplasmic and perinuclear distribution. Results presented herein provide the first experimental evidence showing that CD1d antigen is present on circulating, activated T lymphocytes, suggesting that its expression is dependent on the activation state of the cells. Elucidation of the molecular mechanisms implicated in the activation-dependent expression of this nonclassical antigen will provide new insights into the understanding of antigen presentation and immune regulation.
Differential effects of anti-FcγRIIIb autoantibodies on polymorphonuclear neutrophil apoptosis and function
Authors: Durand Véronique , Pers Jacques-Olivier , Renaudineau Yves , Saraux Alain , Youinou Pierre , Jamin Christophe 
Published: September 2022

AbstractAnti-Fcγ receptor IIIb (FcγRIIIb) human autoantibodies (Ab) have been classified previously into three groups, based on the results of an indirect immunofluorescence (IIF) test and an enzyme-linked immunosorbent assay (ELISA): IIF+/ELISA+ (group A), IIF+/ELISA− (group B), and IIF−/ELISA+ (group C) sera. In this study, differential effects between IIF+ autoAb, recognizing cell-bound FcγR, and those ELISA+, recognizing only cell-free FcγR, were studied on polymorphonuclear neutrophils (PMN). Neither group A nor B autoAb was cytotoxic, although both prolonged the survival of PMN by delaying spontaneous apoptosis. By the same extent, the PMN-binding antisera stimulated the appearance of a CD11bdim population, following a 12-h incubation. This event was associated with a lowered expression of β2 integrin molecules, resulting in altered PMN function. Treatment with groups A and B autoAb reduced adhesiveness and respiratory burst. This impairment of the responses was more pronounced when the cells originated from donors NA1+NA1+ rather than donors NA2+NA2+. From our observations, the influences of anti-FcγRIIIb autoAb on PMN survival, as well as function and subsequent dysregulation of the inflammatory response, have proven somewhat dependent on their target antigens, as determined by IIF coupled with ELISA and FcγRIIIb polymorphism.
CpG-containing oligodeoxynucleotides induce TNF-α and IL-6 production but not degranulation from murine bone marrow-derived mast cells
Authors: Zhu Fu-Gang , Marshall Jean S 
Published: September 2022

AbstractMast cells are sentinel cells critical to the initiation of innate immune and inflammatory responses, particularly at mucosal surfaces. To fulfill this function they can be activated by several pathogen-associated stimuli to produce cytokines with or without concurrent degranulation. We examined the ability of immunostimulatory DNA sequences including CpG motifs, which are found in increased quantities in bacterial DNA, to activate mouse bone marrow-derived mast cells (mBMMC). Mast cells were treated with a range of doses of CpG-containing oligodeoxynucleotides or control oligodeoxynucleotides without CpG within their sequence. There was a dose-dependent increase in the production of both interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) by mast cells treated with the CpG-containing oligodeoxynucleotides. The cytokine levels induced were directly related to the number of CpG within a given length of sequence. Treatment with oligonucleotides containing 3CpG induced an eightfold increase in TNF production over control incubated mast cells. Other cytokines, including granulocyte-macrophage colony-stimulating factor, IL-4, interferon-γ, and IL-12 were not induced by oligonucleotide treatment. Neither CpG containing oligodeoxynucleotides nor control oligodeoxynucleotides induced degranulation of mast cells. Bacterial DNA from Escherichia coli also induced IL-6 from mBMMC but neither calf thymus DNA nor methylase-treated E. coli DNA had such an effect. Examination of the uptake of Texas red-labeled CpG and non-CpG-containing oligodeoxynucleotides revealed that they were both similarly taken up by the mBMMC. These results have important implications for the mechanism by which mast cells respond to bacteria and for the potential role of mast cells in DNA vaccination.
Regulation of hematopoiesis through adhesion receptors
Authors: Prosper Felipe , Verfaillie Catherine M 
Published: September 2022

AbstractNormal steady-state hematopoiesis takes place in the bone marrow microenvironment. Soluble factors as well as contact interactions between the hematopoietic cells and the marrow microenvironment dictate the fate of hematopoietic stem cells and progenitors. Over the last decade it has become clear that cell-cell and cell-extracellular matrix interactions through adhesion receptors play a major role in the hematopoietic process. They are required for the residence of stem cells and progenitors in the marrow, as well as for homing of stem and progenitor cells to the marrow in the setting of stem cell transplantation. Furthermore, adhesion receptors play an important role in regulation of cell behavior, either through direct activation of signal pathways important for cell survival, cell growth, and cell fate decision-making processes, or by modulating responses to growth factors. Insights in the abnormalities seen in these interactions in diseases of the hematopoietic system will help to develop better therapeutic strategies based on the pathogenesis of these diseases.
Lymphoid neogenesis:de novoformation of lymphoid tissue in chronic inflammation through expression of homing chemokines
Authors: Hjelmström Peter 
Published: September 2022

AbstractChronic inflammation is a complex pathophysiological process with accumulation of mononuclear cells seen in response to invading pathogens, neoplastic transformation, or autoimmune recognition of self-antigens. The inflammatory process has evolved to facilitate effective elimination of pathogens and tumors and it is normally transient and turned off when the causative stimulus has been eliminated. Occasionally, however, the process is sustained for a long time and can lead to severe tissue damage. This is seen in organ-specific autoimmune diseases such as rheumatoid arthritis, Sjögren's syndrome, and Hashimoto's thyroiditis, but also in infectious diseases such as Helicobacter pylori-induced gastritis. Disturbingly, many of these chronic inflammatory diseases are associated with an increased risk for neoplastic transformation and development of lymphomas. This review summarizes experimental evidence suggesting that chronic inflammation involves ectopic de novo formation of organized lymphoid tissue and that this lymphoid neogenesis is regulated by expression of homing chemokines.
DNA damage and apoptosis in mononuclear cells from glucose-6-phosphate dehydrogenase-deficient patients (G6PD Aachen variant) after UV irradiation
Authors: Efferth Thomas , Fabry Ursula , Osieka Rainhardt 
Published: September 2022

AbstractPatients affected with X chromosome-linked, hereditary glucose-6-phosphate dehydrogenase (G6PD) deficiency suffer from life-threatening hemolytic crises after intake of certain drugs or foods. G6PD deficiency is associated with low levels of reduced glutathione. We analyzed mononuclear white blood cells (MNC) of three males suffering from the German G6PD Aachen variant, four heterozygote females of this family, one G6PD-deficient male from another family coming from Iran, and six healthy male volunteers with respect to their DNA damage in two different genes (G6PD and T-cell receptor-δ) and their propensity to enter apoptosis after UV illumination (0.08–5.28 J/cm2). As determined by PCR stop assays, there was more UV-induced DNA damage in MNC of G6PD-deficient male patients than in those of healthy subjects. MNC of G6PD-deficient patients showed a higher rate of apoptosis after UV irradiation than MNC of healthy donors. MNC of heterozygote females showed intermediate rates of DNA damage and apoptosis. It is concluded that increased DNA damage may be a result of deficient detoxification of reactive oxygen species by glutathione and may ultimately account for the higher rate of apoptosis in G6PD-deficient MNC.
Importance of CD44v7 isoforms for homing and seeding of hematopoietic progenitor cells
Authors: Christ Oliver , Günthert Ursula , Haas Rainer , Zöller Margot 
Published: September 2022

AbstractThe adhesion molecule CD44 consists of many isoforms of which particularly CD44v7 is of major importance in hematopoietic progenitor cell homing. An increase of progenitor cells in the periphery was observed after treating mice with a CD44v7-specific antibody, concomitant with a substantially augmented marrow-repopulating ability (MRA). Because CD44v7 is expressed on a fraction of bone marrow cells (BMC) as well as on long-term bone marrow culture-derived stromal cells, we aimed to differentiate between the functional relevance of CD44v7 on either cell type by transferring CD44v7+/+ BMC into CD44v7-/- mice and vice versa. CD44v7+/+ BMC homed poorly in the bone marrow of CD44v7-/- mice and their MRA was severely impaired. CD44v7-/- BMC, instead, exhibited an improved MRA when transferred into the CD44v7+/+ host, although their MRA remained below that of CD44v7+/+ BMC. Thus, it is predominantly, but not exclusively, expression of CD44v7 on stromal cells which supports progenitor cell homing.
MHCII,Tlr4andNramp1genes control host pulmonary resistance against the opportunistic bacteriumPasteurella pneumotropica
Authors: Chapes Stephen K , Mosier Derek A , Wright Albion D , Hart Marcia L 
Published: September 2022

AbstractMHCII, Tlr4, and Nramp1 genes are each independently important in pulmonary immunity. To determine the effect of these genes on host resistance, mice carrying various combinations of functional alleles for these three genes were experimentally challenged with the opportunistic bacterium, Pasteurella pneumotropica. MHCII-/-,Tlr4d/d, and Nramp1s/s mice were significantly more susceptible to experimental infections byP. pneumotropica after intranasal challenge compared to mice carrying functional alleles at only one of those genes. P. pneumotropica were cultured from the lungs of challenged mice, and the severity of the pneumonia strongly correlated with the number of isolated bacteria. Mice with the genotype MHCII-/-Tlr4n/n genotype were less susceptible to pneumonia than MHCII+/+, Tlr4d/d mice. It is interesting that the Nramp1 gene contribution to host resistance was apparent only in the absence of functional MHCII or Tlr4 genes. These data suggest that MHCII,Tlr4, and Nramp1 genes are important to pulmonary bacterial resistance.
A p74 common gamma receptor chain isoform facilitates IL-2 and IL-15 responses by the myelomonocytic cell line Tf-1β2
Authors: Monson Nancy L , Fenske Timothy J , Wei Shyng , Okragly Angela J , de Jong Jill L O , Haak-Frendscho Mary , O'Shea John , Djeu Julie , Sondel Paul M 
Published: September 2022

AbstractFunctional forms of the IL-2, IL-4, IL-7, IL-9, and IL-15 receptors require the γc receptor component. We have described previously a myeloid cell line called Tf-1β, which binds IL-2 with intermediate-affinity and proliferates in response to IL-2. In this study, we characterize γc expression on Tf-1β2 cells, a derivative of Tf-1β cells stimulated exclusively with IL-2. Although Tf-1β2 cells bind IL-2 with intermediate-affinity and proliferate in response to IL-2, this cell line does not express the p64 γc chain at the protein level. This result was surprising because prior studies suggest these cells should not be expected to proliferate in response to IL-2 or IL-15 in the absence of the p64 γc chain. A p74 protein was detected by western blot following immunoprecipitation with an anti-γc polyclonal antibody, and a p74 protein was identified consistently in complex with IL-2 and IL-15 on these cells. However, the γc gene in these Tf-1β2 cells shows no evidence of mutation by sequence analysis. Furthermore, inhibition of glycosylation of these Tf-1β2 cells by tunicamycin treatment yields a standard 39-kDa molecule recognized on western blot with anti-γc antibody, as seen for the standard 64-kDa isoform of γc. These results demonstrate that a 74-kDa γc receptor isoform was involved in the response of the Tf-1β2 cells to cytokines which normally interact with the 64-kDa γc chain.
SJL and NOD macrophages are uniquely characterized by genetically programmed, elevated expression of the IL-12(p40) gene, suggesting a conserved pathway for the induction of organ-specific autoimmunity
Authors: Alleva David G , Johnson Eric B , Wilson Jerry , Beller David I , Conlon Paul J 
Published: September 2022

AbstractGenetic susceptibility of the SJL mouse to experimental autoimmune encephalomyelitis (EAE) appears, in part, to be a result of genes that promote abnormal development of the pathogenic Type 1 (Th1) phenotype of neuroantigen-specific T-cells. Because antigen-presenting/accessory cells (APCs) produce cytokines that can modulate the development of Th1 and Th2 phenotypes, we addressed whether APCs from SJL mice were genetically programmed for elevated expression of the Th1-promoting cytokine, IL-12. Activated peritoneal macrophages (Mφ; i.e., APC) from naïve SJL mice produced levels of TNF-α, IL-1, IL-6, IL-10, and TGF-β within the range of six normal strains. In contrast, SJL IL-12p40 (in addition to IL-12p70) production was consistently five- to 20-fold greater than that of any normal strain tested, which arose from elevated expression of the IL-12p40 but not the IL-12p35 gene, because p40 mRNA levels were eight- to 15-fold greater than those of normal strains. This aberrancy in IL-12p40 expression appears identical to that observed in the NOD mouse, another strain prone to organ-specific autoimmunity. A genetically programmed bias toward elevated expression of IL-12 in Mφ from the SJL and NOD strains of autoimmunity provides a conserved mechanism for the dominant Th1 development of naïve, autoantigen-specific T-cells in these strains. This study is the first demonstration of a genetically programmed aberrant phenotype that is intrinsically expressed within a cell type in the SJL mouse and provides insight into its predisposition for EAE.
Differential expression of Toll-like receptor 2 in human cells
Authors: Flo Trude H , Halaas Øyvind , Torp Sverre , Ryan Liv , Lien Egil , Dybdahl Brit , Sundan Anders , Espevik Terje 
Published: September 2022

AbstractHuman Toll-like receptor 2 (TLR2) is a receptor for a variety of microbial products and mediates activation signals in cells of the innate immune system. We have investigated expression and regulation of the TLR2 protein in human blood cells and tissues by using two anti-TLR2 mAbs. Only myelomonocytic cell lines expressed surface TLR2. In tonsils, lymph nodes, and appendices, activated B-cells in germinal centers expressed TLR2. In human blood, CD14+ monocytes expressed the highest level of TLR2 followed by CD15+ granulocytes, and CD19+ B-cells, CD3+ T-cells, and CD56+ NK cells did not express TLR2. The level of TLR2 on monocytes was after 20 h up-regulated by LPS, GM-CSF, IL-1, and IL-10 and down-regulated by IL-4, IFN-γ, and TNF. On purified granulocytes, LPS, GM-CSF, and TNF down-regulated, and IL-10 modestly increased TLR2 expression after 2 h. These data suggest that TLR2 protein expression in innate immune cells is differentially regulated by inflammatory mediators.
Inhibition of FasL sustains phagocytic cells and delays myogenesis in regenerating muscle fibers
Authors: Sandri Marco , Sandri Claudia , Brun Barbara , Giurisato Emanuele , Cantini Marcello , Rossini Katia , Destro Chiara , Arslan Paola , Carraro Ugo 
Published: September 2022

AbstractMacrophage-muscle cell interactions are complex, and the majority is unknown. The persistence of inflammatory cells in skeletal muscle could be critical for myofiber viability. In the present paper, we show that FasL plays a role in the resolution of muscle inflammation. We analyzed inflamed muscles of normal mice treated from day 3 to day 8 with a FasL inhibitor (Fas-Ig) or with control Ig. Treated muscles were collected at 3, 5, and 10 days. The treatment with recombinant Fas-Ig protein induced a severe persistence of inflammatory cells at 5 days (115,000±27,838 vs. 41,661±6848, p&lt;0.01) and 10 days from injury (145,500±40,850 vs. 5000±1000, p&lt;0.001). Myofiber regeneration was highly impaired (37±14 vs. 252±28, p&lt;0.01). Apoptosis of phagocytic cells was absent during Fas-Ig treatment (0.9±0.6 vs. 1300±150,p&lt;0.0001), but apoptotic, mononucleated cells appeared at day 10, 2 days after the suspension of Fas-Ig administration. The time course of FasL expression during muscle inflammation, at mRNA and protein level, reveals a peak during myoblast proliferation. The peak of FasL expression coincides with the peak of apoptosis of phagocytic cells. In situ hybridization shows the co-expression of FasL and MyoD mRNA in mononucleated cells, i.e., myoblasts. Experiments on the myoblast cell culture confirmed the expression of FasL in myoblasts. The findings shown here indicate one of the pathways to control myoblast-macrophage interaction and might be relevant for the control of inflammatory cells in muscle tissue. Perhaps altering FasL expression with recombinant proteins could ameliorate inflammation in degenerative myopathies and up-regulate muscle regeneration.