bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monoclonal antibodies from NZW x BXSB F1 mice to beta2 glycoprotein I and cardiolipin. Species specificity and charge-dependent binding.
Authors: Monestier M , Kandiah D A , Kouts S , Novick K E , Ong G L , Radic M Z , Krilis S A 
Published: January 2023

Abstract
NZW x BXSB F1 mice develop a systemic autoimmune syndrome with various lupus-like manifestations. Male animals develop a degenerative coronary disease with myocardial infarction, resulting in death before 6 mo of age. The presence in these mice of anti-phospholipid Abs reacting with beta2-glycoprotein I may contribute to the pathogenesis of the cardiovascular lesions. beta2-glycoprotein I, a plasma protein implicated in various aspects of the coagulation pathway, is also the target of autoantibodies in humans with the anti-phospholipid syndrome. We obtained several mAbs from NZW x BXSB F1 mice that were selected for binding to cardiolipin. Two mAbs are specific for beta2-glycoprotein I and display a species-dependent pattern with preferential reactivity to mouse beta2-glycoprotein I. The other mAbs display charge-mediated interactions with anionic phospholipids in the absence of beta2-glycoprotein I. The analysis of the V region sequences of the mAbs suggests that cationic residues in the H chain complementarity-determining region 3 are important for their phospholipid reactivity. The structural features of the V(H)-D-J(H) junctions of these mAbs further support the view that an increased frequency of unusual V(D)J rearrangements directly contributes to the development of murine autoimmunity.
IFN-gamma plays a critical down-regulatory role in the induction and effector phase of myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis.
Authors: Willenborg D O , Fordham S , Bernard C C , Cowden W B , Ramshaw I A 
Published: January 2023

Abstract
129/Sv mice are resistant to induction of experimental autoimmune encephalomyelitis (EAE) induced with myelin oligodendrocyte glycoprotein peptide (MOG35-55). Mice of this strain lacking the gene coding for the ligand-binding chain of the IFN-gamma receptor develop EAE with high morbidity and mortality. Spleen cells from sensitized IFN-gammaR-/- mice proliferated extensively when stimulated with MOG peptide in culture and produced high levels of IFN-gamma and TNF but no detectable IL-4. Transfer of spleen cells from sensitized IFN-gammaR-/- mice produced EAE in both IFN-gammaR+/+ and IFN-gammaR-/- recipients. Disease was severe in IFN-gammaR-/- recipients and mortality high (77%). Surviving mice remained moribund until termination of the experiments. IFN-gammaR+/+ recipients developed disease of equal severity, but with no mortality, and recovered significantly. These results indicate that IFN-gamma is not essential for the generation or function of anti-MOG35-55 effector cells but does play an important role in down-regulating EAE at both the effector and induction phase of disease.
Enterotoxin septic shock protection and deficient T helper 2 cytokine production in growth hormone transgenic mice.
Authors: Gonzalo J A , Mazuchelli R , Mellado M , Frade J M , Carrera A C , von Kobbe C , Merida I , Martinez-A C 
Published: January 2023

Abstract
Neuroendocrine hormones have long been thought to play a role in lymphoid development and function. In particular, growth hormone has been shown to mediate thymic development as well as to promote T cell engraftment in severe combined immunodeficiency mice. Murine T helper cells are classified into two subsets based on their cytokine production pattern. Here, we report that transgenic mice for bovine growth hormone show significant alterations in T cell function and decreased capability for cytokine production, an effect that is more acute in T helper cells as measured by their inability to produce IL-4 upon in vivo injection with Staphylococcus aureus enterotoxin B. Furthermore, upon immunization with conventional Ags, growth hormone transgenic mice produce an altered Ig isotype pattern characterized by a response shift from IgG1 in nontransgenic mice to IgG2 in transgenic mice. The impaired T cell responses correlated with survival from septic shock mediated by bacterial enterotoxins. We conclude that growth hormone may have the potential of regulating immune responses in pathologic processes associated with hyperactivation of T cells or with massive cytokine production.
The xid mutation diminishes memory B cell generation but does not affect somatic hypermutation and selection.
Authors: Ridderstad A , Nossal G J , Tarlinton D M 
Published: January 2023

Abstract
In this study, we examine the relationship between primary and secondary T cell-dependent immune responses using the response of xid mice to the hapten (4-hydroxy-3-nitrophenyl)acetyl (NP) as an experimental model. The reduced serologic primary immune response of xid mice was demonstrated to be caused by a substantially decreased Ab-forming cell (AFC) generation. Furthermore, the germinal center reaction in the primary xid immune response was diminished and the frequency of NP-specific memory B cells prior to secondary immunization was reduced 10-fold. Despite the poor primary response of xid mice, secondary exposure to Ag generated a response that was qualitatively and quantitatively equal to that of wt mice. The number of IgG1 AFCs in spleen and bone marrow increased equally in both groups, as did the proportion of AFCs secreting high affinity Ab in both locations. The extent and distribution of somatic mutations in the V(H) genes of xid secondary response B cells was also found to be normal, indicating that the xid gene product is not critical for the processes that result in affinity maturation. Thus, although xid mice generate memory B cells of normal phenotype but at a substantially lower frequency, this does not limit the magnitude of the secondary response. Therefore, our results imply that the reduced memory B cell frequency in xid mice is still above some threshold value necessary for a normal secondary immune response.
Postinduction transcriptional repression of E-selectin and vascular cell adhesion molecule-1.
Authors: Read M A , Neish A S , Gerritsen M E , Collins T 
Published: January 2023

Abstract
TNF-alpha induction of the E-selectin and vascular cell adhesion molecule-1 (VCAM-1) genes leads to transient accumulation of high levels of mRNA in endothelial cells. The increase in these mRNAs after induction is due to an increase in the rate of gene transcription, which is maintained for several hours in the continuous presence of cytokine. Cytokine-induced transcriptional activation of these genes requires the transcription factor, nuclear factor-kappaB. Following removal of TNF-alpha, there is rapid postinduction transcriptional repression common to both of these genes. The repression is protein synthesis dependent and correlates with protein synthesis-dependent loss of both the p50 and p65 subunits of nuclear factor-kappaB from the nucleus. IkappaBalpha is capable of specifically displacing endothelial-derived heterodimeric p50/p65 from the E-selectin and VCAM-1 kappaB elements, while having no effect on binding of p50 homodimer. In the presence of agents that block proteasomal degradation of IkappaBalpha, endogenous IkappaBalpha can be visualized in the nucleus of both resting and TNF-alpha-activated endothelial cells. Endogenous IkappaBalpha is readily detected in the nucleus of HeLa cells, and its nuclear localization is increased following removal of TNF-alpha. Repression of E-selectin and VCAM-1 transcription following cytokine removal requires the loss of nuclear p50 and p65, and involves IkappaBalpha. This postinduction transcription repression mechanism may be one component of a program that prevents inappropriate and prolonged expression of adhesion molecules.
Persistent cytokine expression in trigeminal ganglion latently infected with herpes simplex virus type 1.
Authors: Halford W P , Gebhardt B M , Carr D J 
Published: January 2023

Abstract
Following ocular infection, herpes simplex virus type 1 (HSV-1) establishes latency in trigeminal ganglion (TG) neurons. Using reverse transcription-PCR, cytokine gene expression was analyzed in the TGs of mice infected with HSV-1. IL-2, TNF-alpha, IFN-gamma, IL-10, and RANTES mRNAs were readily detected in TGs taken from mice 7 days postinoculation (PI). Likewise, IL-2, IL-6, IL-10, and IFN-gamma protein were detected by ELISA of TG homogenates. Between 5 and 45 days PI, IL-10, IFN-gamma, TNF-alpha, and RANTES mRNAs were detected in nearly 100% of latently infected TGs (latent infection was confirmed by reverse transcription-PCR detection of HSV-1 latency-associated transcripts). T cell-associated cytokine and chemokine mRNAs (IL-2, IL-10, IFN-gamma, and RANTES) were still detected in the majority of latently infected TG samples taken between 60 and 135 days PI. In contrast, these cytokine mRNA species were rarely detected in uninfected TGs. Measurement of serum Abs to HSV-1 at different times revealed that anti-HSV-1 Ab concentrations approached a plateau in mice by 30 days PI but remained at high levels 67 and 125 days PI. Although there was molecular evidence of an ongoing immune response to HSV-1 in latently infected TG, histologic analysis indicated that very few mononuclear cells remained in the ganglion 60 days PI. Collectively, the results suggest that residual lymphocytes encounter viral Ag during HSV-1 latency with sufficient frequency to remain activated. The paradox of a persistent immune response against a latent infection is discussed.
Transcriptional up-regulation of intracellular adhesion molecule-1 in human endothelial cells by the antioxidant pyrrolidine dithiocarbamate involves the activation of activating protein-1.
Authors: Muñoz C , Castellanos M C , Alfranca A , Vara A , Esteban M A , Redondo J M , de Landázuri M O 
Published: January 2023

Abstract
The redox status of the cell plays an essential role in regulating signal transduction, transcription factor activity, and expression of cell surface molecules. In this study, we show that pyrrolidine dithiocarbamate (PDTC), a potent antioxidant agent, upregulated the cell surface expression of intercellular adhesion molecule-1 (ICAM-1) in human endothelial cells (EC). Further analysis of PDTC-mediated ICAM-1 up-regulation revealed that PDTC increased ICAM-1 mRNA levels and augmented its gene promoter activity. Transfection experiments in EC with reporter constructs harboring nested deletion fragments of the ICAM-1 promoter indicated the presence of a functional PDTC-responsive region located between positions -136 to -353 of the promoter. Gel retardation assays together with supershift analysis revealed that PDTC induced the binding of c-fos and c-jun to a consensus activating protein-1 (AP-1) binding site located at position -284. PDTC alone or in combination with TNF-alpha enhanced AP-1-dependent transactivation in HUVEC, as determined by DNA binding assays. The functional implication of AP-1 in the transcription of the ICAM-1 gene was further demonstrated by cotransfection experiments in which a c-jun expression vector induced the promoter activity of the PDTC-responsive element of the ICAM-1 promoter. Taken together, these results indicate that the antioxidant PDTC induces transcriptional activation of ICAM-1 and that this induction is mediated at least in part by the transcription factor AP-1. This mechanism might be operative in pathologic conditions in which a redox imbalance plays a key role, such as ischemia/reperfusion injury or arteriosclerosis.
Regulation of polymorphonuclear leukocyte cytokine receptor expression: the role of altered oxygen tensions and matrix proteins.
Authors: Simms H , D'Amico R 
Published: January 2023

Abstract
We investigated the effects of hypoxemia +/- reoxygenation (H/R) on matrix protein regulation of polymorphonuclear leukocyte (PMN) IL-1beta types I and II, TNF-alpha (p60, p80), and IL-8R expression compared with normoxic controls. H/R reduction IL-1beta type I, TNF-alpha (p80), and IL-8R expression compared with hypoxic levels. Neither fibronectin nor laminin effected cytokine receptor expression during normoxia, but both fibronectin and laminin significantly reduced IL-1beta type I, TNF-alpha (p80), and IL-8R expression during hypoxia. Following H/R, both fibronectin and laminin significantly reduced IL-1beta type I, TNF-alpha (p80), and IL-8R expression during hypoxia. Following H/R, both fibronectin and laminin significantly increased TNF-alpha (p60, p80) and IL-8R expression. Cross-linking of adherent PMN very late antigen (VLA)-5 and VLA-6 receptors resulted in a progressive increase in TNF-alpha (p60, p80) and IL-8R expression during hypoxia; cross-linking of adherent PMN VLA-5 and and VLA-6 receptors resulted in a progressive increase in TNF-alpha (p60, p80) and IL-8 receptors following H/R. Cross-linkage of IL-1betaR type I, TNF-alphaR (p80), and IL-8R during hypoxia and H/R resulted in increased and subsequently decreased O2- production and degranulation. Inhibition of reduced nicotinamide adenine dinucleotide phosphate oxidase activation with diphenyleneiodonium following hypoxia but before reoxygenation prevented the decreases in IL-1beta types I and II, TNF-alpha (p80), and IL-8R expression that was seen following H/R alone. These results demonstrate that, during hypoxia and H/R, integrin signaling via alpha5beta1, and alpha6beta1 increases and subsequently decreases the expression of PMN cytokine receptors.
Adenoviral gene delivery elicits distinct pulmonary-associated T helper cell responses to the vector and to its transgene.
Authors: van Ginkel F W , McGhee J R , Liu C , Simecka J W , Yamamoto M , Frizzell R A , Sorscher E J , Kiyono H , Pascual D W 
Published: January 2023

Abstract
Replication-deficient adenovirus (Ad) vectors are effective to specifically target the respiratory epithelium for either corrective gene therapy such as cystic fibrosis or for mucosal immunization. As a consequence of transducing the lower respiratory tract with an E1/E3 deleted Ad5 vector, host responses have been characterized by the duration of transgene expression and by the induction of CTL responses. However, limited emphasis has been devoted to understanding the contribution of CD4+ T cell responses to the Ad vector. Both CD4+ and CD8+ T cells migrate into the lung following sequential intratracheal Ad5 transgene instillations. Isolated CD3+ T lymphocytes from the lungs were predominantly of the Th2 type, and after cell sorting, the IL-4-producing T cells were largely CD4+, while IFN-gamma expression was associated with both CD4+ and CD8+ T cells. Ab responses to the Ad5 vector and to the expressed transgene beta-galactosidase (beta gal) revealed elevated bronchial and serum IgA and IgG Abs with low neutralization titers. Analysis of serum IgG subclass responses showed IgG1 and IgG2b with lower IgG2a Abs to Ad5 and IgG2a and IgG2b Ab responses to beta gal. Ad5-specifc CD4+ T cells produced both Th1 (IFN-gamma and IL-2)- and Th2 (IL-4, IL-5, IL-6)-type cytokines, while beta gal-specific CD4+ T cells secreted IFN-gamma and IL-6. This study provides direct evidence for the concomitant induction of Th2- with Th1-type responses in both the pulmonary systemic and mucosal immune compartments to the Ad5 vector as well as a Th1-dominant response to the transgene.
Structural analysis of human antibodies to proteinase 3 from patients with Wegener granulomatosis.
Authors: Sibilia J , Benlagha K , Vanhille P , Ronco P , Brouet J C , Mariette X 
Published: January 2023

Abstract
We determined the structure of five IgM autoAbs to proteinase-3 (PR3). These Abs are highly specific for Wegener's granulomatosis (WG) and may be involved in the pathogenesis of vasculitis in WG. Five clonal lymphoblastoid cell lines secreting Abs to PR3 were derived from four patients' B cells. From 3 to 5% of supernatants from wells contained detectable anti-PR3 Abs, indicating that anti-neutrophil cytoplasmic Ab specificity represents a sizable part of the IgM B cell repertoire in patients with WG. Mu heavy chains of WG1, WG4-1, and WG4-2 clones belonged to the VH3 subgroup. WG4-1 and WG4-2 heavy chains were identical, indicating an oligoclonal expansion of autoreactive B cells in this patient. WG4-1 (and WG4-2) used the VH3-23 V(H) gene, the product of which was shown to directly bind PR3. Heavy chains of WG2 and WG3 derived from VH4-59 and VH1-2 genes, respectively. Comparison with germline sequences showed that three of the five V(H) genes from clonal lines were somatically mutated with a R:S ratio in complementarity-determining regions of 3:0, 5:1, and 5:1, respectively. Three kappa light chains derived from the Vkappa4 gene, and one derived from a Vkappa1 gene. In these four Vkappa genes, there were overall R:S ratios of mutation of 8:1 and 0:7 in complementarity-determining regions and framework regions, respectively. These data suggest that the production of these autoantibodies, which are increasingly important in the diagnosis and management of WG, are influenced by an Ag-driven process.
A cloned chicken lymphokine homologous to both mammalian IL-2 and IL-15.
Authors: Sundick R S , Gill-Dixon C 
Published: January 2023

Abstract
IL-2, cloned in several mammalian species, plays a critical role in immune system function. Indirect evidence suggests that IL-2-like molecules also exist in lower vertebrates, although none has been cloned. In view of the commercial importance of poultry and the lack of any IL-2 sequence data in lower vertebrates, we undertook to clone a chicken IL-2-like molecule. To this end, a cDNA library was constructed from activated chicken spleen cells and screened for T cell proliferative activity. Three clones of a single gene were isolated that produced a protein stimulatory for activated T cell blasts. This protein had 24 to 25% amino acid identity and 44 to 46% similarity to both bovine IL-2 and IL-15. The homology with IL-15 was unexpected, since primate IL-15 was reported to have no homology with IL-2. However, genetic distance analysis indicated that the chicken interleukin homology is closer to the mammalian IL-2 than to the mammalian IL-15 homology. Furthermore, the chicken gene has several characteristics of mammalian IL-2s: e.g., expression only by activated T cells, mRNA with a short 5' region preceding the open reading frame, and a short leader sequence. It has one characteristic that is unique to IL-15: four conserved cysteines allowing for two intrachain disulfide bonds.
The role of gammadelta T lymphocytes in lipopolysaccharide-induced eosinophil accumulation into the mouse pleural cavity.
Authors: Penido C , Castro-Faria-Neto H C , Larangeira A P , Rosas E C , Ribeiro-dos-Santos R , Bozza P T , Henriques M G 
Published: January 2023

Abstract
LPS induces an accumulation of eosinophils in the pleural cavity that requires resident macrophages and lymphocytes, but is independent of IL-5 production. In the present study we investigated the involvement of different T lymphocyte subsets on the modulation of LPS-induced eosinophil accumulation into the pleural cavity of mice. Within 4 h after LPS injection the number of neutrophils in the pleural cavity increased significantly. Mononuclear cell counts increased after 12 h, while a significant rise on eosinophil counts was observed only after 24 h. T lymphocytes counts were increased in the pleural cavity 24 and 48 h after LPS administration. This T lymphocyte accumulation was accounted for by an influx of the gammadelta+ subset, while CD4+ and CD8+ subsets did not accumulate in the pleural cavity after LPS stimulation. All those changes had resolved 96 h after LPS injection. Depletion of T lymphocytes by treatment with mAb anti-Thy 1.0 inhibited the eosinophil accumulation triggered by LPS. Aiming to clarify which T lymphocyte subset would be involved in the LPS-induced eosinophil accumulation, we depleted mice of various T lymphocyte subpopulations using specific Abs. Depletion of either CD4+ or CD8+ subsets failed to inhibit LPS-induced eosinophil migration. In contrast, when mice were treated with anti-gammadelta+ T lymphocyte mAb, a significant reduction of LPS-induced eosinophil accumulation was observed. Similarly, the administration of LPS in BALB/c-nu/nu mice induced the expected significant influx of eosinophils into the pleural cavity. Our results indicate that the gammadelta+ T lymphocytes are centrally involved in LPS-induced eosinophil accumulation in mice.
STAT5 involvement in the differentiation response of primary chicken myeloid progenitor cells to chicken myelomonocytic growth factor.
Authors: Woldman I , Mellitzer G , Kieslinger M , Buchhart D , Meinke A , Beug H , Decker T 
Published: January 2023

Abstract
We have investigated the activation of the STAT5 protein during the differentiation of myelomonocytic cells. In the human U937 promonocytic cell line, STAT5 activation occurred in response to several inducers of monocytic differentiation (phorbol ester, 1alpha,25-dihydroxyvitamin D3, and retinoic acid). In the promyelocytic HL60 cell line, STAT5 was activated in the course of either phorbol ester-induced monocytic differentiation or DMSO-induced granulocytic differentiation. To test for involvement of STAT5 in the differentiation of primary nonimmortalized cells, chicken myeloid progenitor cells transfected with the ts21-E26 avian retrovirus were studied. At 37 degrees C the temperature-sensitive oncoprotein of the ts21-E26 virus (p135(gag-myb-ets)) installs a differentiation block that is released by a shift to the nonpermissive temperature (42 degrees C). Both proliferation and differentiation of ts21-E26-transfected myeloblasts require the continuous presence of chicken myelomonocytic growth factor (cMGF). Addition of cMGF to growth factor-starved cells rapidly caused STAT5 tyrosine phosphorylation, DNA binding, and transcriptional activity at both permissive and nonpermissive temperatures. Moreover, the temperature shift-induced onset of myelomonocytic differentiation strictly correlated with the appearance of activated STAT5 in ts21-E26-infected myeloblasts, but not in cells infected with wtE26 retrovirus. These data position STAT5 in a nuclear signaling cascade induced by the cMGF receptor and suggest a contribution of STAT5 to the process of myelomonocytic differentiation or to the functional changes that accompany the maturation of myeloid progenitor cells to a terminally differentiated stage.
Suppressive effects of recombinant human monokine induced by IFN-gamma (rHuMig) chemokine on the number of committed and primitive hemopoietic progenitors in liquid cultures of CD34+ human bone marrow cells.
Authors: Schwartz G N , Liao F , Gress R E , Farber J M 
Published: January 2023

Abstract
Studies in this report investigated potential hemopoietic suppressive effects of human monokine induced by IFN-gamma (HuMig), a CXC chemokine that is chemotactic for activated lymphocytes. rHuMig was purified from Trichoplusia ni cells after infection with a recombinant baculovirus. The recombinant protein was added to liquid cultures of CD34+ human marrow cells stimulated with IL-3 alone or with both IL-3 and either insulin-like growth factor II (IGF-II) or stem cell growth factor (SCF). The number of committed progenitors, colony-forming units for granulocytes and macrophages (CFU-GM), and primitive progenitors, long term culture-initiating cells (LTC-IC) derived from liquid cultures of CD34+ cells, was determined. rHuMig abrogated the IGF-II-dependent enhancement of CFU-GM and long term culture-initiating cell numbers. Additional studies demonstrated that in liquid cultures of CD34+ cells both rHuMig and IFN-inducible protein-10, another CXC chemokine that is related to HuMig, inhibited the production or expansion of CFU-GM. For a subset of marrows, rHuMig also abrogated SCF enhancement of CFU-GM numbers in cultures of CD34+ cells stimulated with both IL-3 and SCF. These studies are the first to demonstrate that rHuMig can act as a negative regulator of in vitro hemopoiesis, that both rHuMig and IP-10 can suppress an increase in the number of committed progenitors from CD34+ cells, and that chemokines can abrogate hemopoietic stimulatory effects of IGF-II.