bluuebunny/crossref_metadata_2025_split huggingface dataset:
Murine minor histocompatibility antigens detected by helper T cells. Recognition of an endogenous peptide.
Authors: Wettstein P J 
Published: December 2022

Abstract
Minor histocompatibility (H) Ags, encoded by autosomal and sex-linked genes, have classically been identified by the cytolytic T lymphocyte response to class I-bound minor H Ags. A limited number of studies have identified minor H Ags (defined by congenic strains) that stimulate Th cells. We have selected a panel of minor H Ag-specific, CD4+ Th hybrids by the fusion of a BW5147 variant with a C57BL/6 anti-BALB.B T cell line. Studied hybrids secrete IL-2 following stimulation with BALB.B spleen cells and stimulation is blocked with anti-I-Ab Ab. These Th hybrids recognize a minimum of six different Ags (helper T target (HTT)) encoded by independently segregating genes as defined by stimulator cells from 11 CXB recombinant inbred strains. The CXB strain distribution patterns of detected Ags did not match the distribution pattern of the BALB/c MTV6 viral genome indicating that none of the detected Ags were known viral superantigens. Four tested HTT Ags appeared not to be acquired by stimulators as exogenous Ags as BALB.B spleen cells but not a mixture of BALB/c spleen cells and C57BL/6 APC stimulated IL-2 production by the respective Th hybrids. To determine whether Th hybrids recognized peptides bound to I-Ab, I-Ab molecules were immunoprecipitated from the LB27.4 cell line that stimulated the A6.5.5 hybrid (HTT-4 specific). Peptides were extracted from I-Ab molecules, ultrafiltered, and separated by HPLC. A single fraction (with flanking peaks of lower activity) sensitized syngeneic APC to stimulate A6.5.5 hybrid cells; sensitization was observed at pH 5.0 but not pH 7.0, consistent with HTT-4 peptide:I-Ab binding occurring in an endosomal compartment. These observations indicate that at least one class II-restricted minor H Ag is recognized by Th cells as a peptide bound to class II molecules.
Recombination potential of the human DIR elements.
Authors: Moore B B , Meek K 
Published: December 2022

Abstract
The human DIR genes are putative DH elements that are GC rich and are found between DN and DM DH gene segments. The DIR genes each have consensus recombination signal sequences (RSS) that could conceivably generate DIR coding regions of about 126 nucleotides. These RSS should allow for DH-DH rearrangements that do not violate the 12/23 recombination rule. Several Ig CDR3 sequences have been assigned to DIR usage; however, there are frequent gaps and mismatches associated with these assignments. In some instances these CDR3 sequences might be better explained by GC rich N segment addition. This report analyzes the recombination potential of the human DIR elements by PCR. Though DH-JH rearrangement of the DH genes flanking the DIR regions (DM and DN) are easily demonstrated, very little evidence of DIR-JH rearrangement could be documented. Furthermore, in amplifications that should concurrently detect both DH-DIR rearrangements (which maintain the 12/23 recombination rule) and DH-DH rearrangements (which violate the 12/23 recombination rule), DH-DH rearrangements predominate. We conclude that the DIR-associated RSS participate minimally in both DH-DH and DH-JH rearrangement. In addition, we describe several conventional DH-DH rearrangement intermediates, demonstrating unequivocally that this phenomena occurs during human Ig rearrangement.
Characterization of RFM mouse T lymphocyte anti-oncofetal antigen immunity in apparent tumor-free, long-term survivors of sublethal X-irradiation by limiting dilution T lymphocyte cloning.
Authors: Rohrer J W , Culpepper C , Barsoum A L , Coggin J H 
Published: December 2022

Abstract
Fractionated sublethal x-irradiation induces thymic lymphomas in up to 60% of RFM mice by 6 mo after irradiation, but no thymomas arise after 6 mo. All radiation-induced tumors expressed oncofetal Ag (OFA) and thymic OFA expression significantly preceded detectable thymomas. To determine whether lymphoma-free, radiation survivor mice had anti-OFA T cell immunity, we analyzed their clonable 5T lymphoma-reactive T lymphocytes and determined the resistance of such mice to challenge with RFM lymphoma cells. RFM mice that were irradiated 6 to 6.5 mo earlier, but which had no apparent tumors, had no more resistance to OFA+ 5T lymphoma cell challenge than nonirradiated age-matched mice. These mice actually developed maximal tumor incidence significantly faster. Analyses of 5T lymphoma-reactive T cell clones established from RFM mice 11 mo after irradiation, however, suggest that activation of anti-OFA immunity occurred subsequent to irradiation. Previously irradiated RFM mice yielded 257% more tumor-reactive T cell clones/mouse than non-irradiated controls. All clones from both sets of mice specifically proliferated to purified OFA. Each irradiated mouse yielded some clones that proliferated to fivefold lower doses of OFA than did any T cell clones from nonirradiated mice. Only these low-dose OFA-reactive clones responded equally to irradiated 4T and 5T cells by proliferation, IFN-gamma secretion, and target lymphoma cell killing. 4T cells express less OFA/cell than 5T cells. Some noncytotoxic CD8 T cells that inhibited cytotoxic T cell function were cloned only from irradiated RFM mice.
Activation of cAMP-dependent pathways in human airway smooth muscle cells inhibits TNF-alpha-induced ICAM-1 and VCAM-1 expression and T lymphocyte adhesion.
Authors: Panettieri R A , Lazaar A L , Puré E , Albelda S M 
Published: December 2022

Abstract
Asthma is a disease of airway inflammation and hyper-reactivity associated with lymphocytic infiltration in the bronchial submucosa. We recently demonstrated that human airway smooth muscle (ASM) cells express the cell adhesion molecules ICAM-1 and VCAM-1, which are up-regulated by cytokines such as TNF-alpha, and which mediate binding of activated T lymphocytes. In this study, we examined whether an increase in [cAMP]i, presumably via activation of cAMP-dependent protein kinase, modulates TNF-alpha-induced ICAM-1 and VCAM-1 on ASM. We found that treatment of ASM with either forskolin, which directly activates adenylyl cyclase, or with cholera toxin, which activates the heterotrimeric GTP-binding protein, Gs, inhibited TNF-alpha-induced cell adhesion molecule expression. In addition, treatment with either isoproterenol or prostaglandin E2, which activates receptors coupled to Gs and increases [cAMP]i, also inhibited TNF-alpha-induced expression of ICAM-1 and VCAM-1 on ASM. Furthermore, adhesion of activated T cells to TNF-alpha-stimulated ASM was inhibited by treating the ASM cells with either forskolin or PGE2. These data suggest that cAMP-dependent protein kinase activation decreases cytokine-induced expression of cell adhesion molecules on ASM cells, modulates T cell binding to airway myocytes and, thus, suggests novel therapeutic approaches to airway inflammation.
Bone marrow-derived murine mast cells migrate, but do not degranulate, in response to chemokines.
Authors: Taub D , Dastych J , Inamura N , Upton J , Kelvin D , Metcalfe D , Oppenheim J 
Published: December 2022

Abstract
We have determined that several chemokines induce mast cell migration in vitro. This directed migration is dependent on the presence of particular extracellular matrix proteins and the activation status of the cells. Mast cell haptotactic responses were observed in response to various chemokines on vitronectin-, laminin-, and fibronectin-coated filters. Unstimulated mast cells were chemoattracted only by monocyte chemotactic protein-1 and RANTES on vitronectin-coated and, to a lesser extent, laminin-coated filters, whereas IgE-activated mast cells migrated in response to monocyte chemotactic protein-1, regulated on activation normal T expressed and secreted, platelet factor-4, and macrophage inflammatory protein-1 alpha on all three matrix proteins. No significant migration was observed on collagen type IV-coated or uncoated filters. Mast cell migration in response to chemokines on extracellular matrices and its enhancement by IgE-dependent activation provide a mechanism by which cells may be drawn to sites of inflammation. Chemokine-induced mast cell recruitment may be particularly relevant in host defense responses to parasitic infections, allergic reactions, Jones-Mote reactions, and in wound healing.
Glomerular binding activity in MRL lpr serum consists of antibodies that bind to a DNA/histone/type IV collagen complex.
Authors: Bernstein K A , Valerio R D , Lefkowith J B 
Published: December 2022

Abstract
To clarify the pathogenesis of lupus nephritis, we developed an assay that defines a glomerular binding activity (GBA) in both murine and human lupus sera highly correlated with nephritis. In the current study, we used a cross-adsorption strategy to establish that the GBA in MRL lpr serum binds to the glomerular basement membrane (GBM). We subsequently observed that this binding to the GBM was competitively inhibited by either exogenous DNA or histone, abrogated by pretreatment of the GBM with DNAse, and restored after DNase treatment with DNA/histone in a synergistic fashion. GBM binding was also completely inhibited by pretreatment of GBM with collagenase but not heparatinase. The effect of collagenase was not reversed by the subsequent addition of DNA, but was restored by the sequential re-addition of type IV collagen and DNA. By using purified basement membrane components, we found that MRL lpr serum bound avidly to DNA coated on type I collagen but less well (or not at all) to DNA coated on type IV collagen, laminin, or fibronectin. Histone pretreatment of type IV collagen before DNA addition, however, synergistically enhanced binding in a fashion similar to that seen with native GBM. Thus, the GBA in MRL lpr serum seems to be comprised of autoantibodies that bind to histones and/or DNA that adhere to type IV collagen within the GBM. These data support the planted Ag hypothesis as the principal pathogenic mechanism in lupus nephritis and suggest that multiple autoantibodies may contribute to this disorder.
Mucosal imbalance of IL-1 and IL-1 receptor antagonist in inflammatory bowel disease. A novel mechanism of chronic intestinal inflammation.
Authors: Casini-Raggi V , Kam L , Chong Y J , Fiocchi C , Pizarro T T , Cominelli F 
Published: December 2022

Abstract
The etiology and pathogenesis of inflammatory bowel disease (IBD) are unknown. Increasing evidence supports the theory that chronic IBD is the result of dysfunctional immunoregulation manifested by an inappropriate production of mucosal cytokines. The aim of the present study was to test the hypothesis that a specific mucosal imbalance of IL-1 and IL-1 receptor antagonist (IL-1ra) production plays an important role in the perpetuation and chronicity of intestinal inflammation. Total IL-1, IL-1ra, and the IL-1ra/IL-1 ratio were measured in freshly isolated intestinal mucosal cells, as well as in mucosal biopsies obtained from control, Crohn's disease, and ulcerative colitis patients. IL-1 alpha, IL-1 beta, and IL-1 ra were measured by specific non-cross-reacting radioimmunoassays and ELISA. A markedly significant decrease in the intestinal mucosal IL-1ra/IL-1 ratio was found in both Crohn's disease and ulcerative colitis patients when compared with control subjects (p &lt; 0.01). The IL-1ra/IL-1 ratio correlated closely with the clinical severity of disease (r = -0.7846, p &lt; 0.001). Furthermore, the observed decrease in the IL-1ra/IL-1 ratio was specific for IBD because a decreased IL-1ra/IL-1 ratio was not found in patients with self-limiting colitis. These results support the hypothesis that an imbalance between IL-1 and IL-1ra production is of pathogenic importance in chronic inflammatory diseases, including IBD.
Breaking tolerance leads to autoantibody production but not autoimmune liver disease in hepatitis B virus envelope transgenic mice.
Authors: Wirth S , Guidotti L G , Ando K , Schlicht H J , Chisari F V 
Published: December 2022

Abstract
Hepatitis B virus (HBV) transgenic mice containing the HBV envelope open reading frame under the transcriptional control of the mouse albumin promoter express hepatitis B surface Ag (HBsAg) in all of their hepatocytes and secrete HBsAg (10 to 40 ng/ml) into the circulation. Because these transgenic mice show no signs of spontaneous liver cell injury or autoimmunity toward the viral (self-) Ag, we asked whether the state of self-tolerance could be reversed by the induction of an acute necroinflammatory liver disease or by immunization with HBV envelope proteins, with the aim of creating a transgenic model for chronic, immune-mediated hepatitis. Our studies indicate that repetitive administration of bacterial LPS, IFN-gamma, or HBsAg-specific CTL, all of which were previously shown to cause liver cell injury and inflammation, does not break tolerance at the T or B cell level, suggesting that the intrahepatic lymphomononuclear cell infiltrate induced by these agents consists of HBsAg-nonspecific cells. The adoptive transfer of HBsAg-primed nontransgenic CD4+ T cells into transgenic mice did not induce anti-HBs autoantibody production by transgenic B cells, even though transgenic B cells were fully responsive to immunization with HBsAg when appropriate T cell help was provided in a nontransgenic environment. Immunization of transgenic mice with purified HBsAg in CFA and repetitive infection with rHBV envelope vaccinia virus led to production of T cell-dependent anti-HBs autoantibodies that cleared HBsAg from the serum, but not to activation of HBsAg-specific CTL. We conclude that HBV envelope transgenic mice are largely tolerant to the transgene product at the T cell but not at the B cell level, and that the activation of an anti-HBs response was not sufficient to induce an autoimmune liver disease in this HBV envelope transgenic mouse model.
Hybrid and allogeneic resistance to T cell grafts mediated by murine NK and CD8+ T cells.
Authors: Davenport C , Haile A , Kumar V , Bennett M 
Published: December 2022

Abstract
Lethally irradiated mice can reject H-2 allogeneic or parental strain stem cells in bone marrow cell (BMC) grafts within 48 h after transplantation. This rapid rejection of BMC grafts occurs without prior sensitization and is mediated by NK1.1+ NK cells. One hypothesis to account for the ability of host NK cells to mediate acute rejection of allogenic and parental stem cells is that these effector cells recognize hemopoietic histocompatibility (Hh-1) Ags on the donor stem cells. T cells present in the donor BMC can prevent NK cell-mediated rejection. However, lethally irradiated mice can also reject T cells present in lymph node cell preparations that respond to alloantigens of the host. T cell grafts from H-2k/Hh-1k, H-2r/Hh-1null, and H-2ia1/Hh-1null donors were rejected by CD8+ NK1.1- T cells. Ags other than Hh-1 Ags appeared to be recognized by these CD8+ T cells. In contrast, host NK cells rejected H-2d/Hh-1d T cell grafts, whereas both NK cells and CD8+ TCR-alpha beta + T cells rejected H-2b/Hh-1b T cell grafts. Therefore, both CD8+ TCR-alpha beta T cells and NK cells mediate allogeneic and hybrid resistance to T cell grafts.
Distinct differentiative stages of CD4+CD8+ thymocyte development defined by the lack of coreceptor binding in positive selection.
Authors: Dutz J P , Ong C J , Marth J , Teh H S 
Published: December 2022

Abstract
Cortical CD4+CD8+ thymocytes mature into CD4+ or CD8+ thymocytes through a process termed positive selection. To better define differentiative stages of CD4+CD8+ thymocyte development in positive selection, we performed a phenotypic analysis of CD4+CD8+ thymocytes from H-Y mice mated to various genetic backgrounds. We have previously shown that coordinate binding of the H-Y TCR and the CD8 coreceptor to the restricting Db MHC class I molecule is required for the efficient positive selection of this TCR. In this study we have used TCR, CD5, and CD45 expression levels as markers for thymocyte maturation. Lack of CD8/Db interaction was achieved by introducing a mutation that abrogates CD8 binding in the alpha 3 domain of Db. We found that the absence of coreceptor ligation prevented TCR up-regulation in CD4+CD8+ thymocytes and resulted in a developmental arrest characterized by low levels of TCR and CD45. We have previously shown that deletion of CD4+CD8+ thymocytes expressing the H-Y TCR is facilitated by CD8 coreceptor ligation. Here we show that expression of the deleting ligand in the absence of coreceptor ligation caused CD5 up-regulation without concomitant TCR or CD45 up-regulation in CD4+CD8+ thymocytes. In a beta 2-microglobulin null background, introduction of the H-Y TCR caused the majority of CD4+CD8+ thymocytes to express an unusually low level of of the CD5 activation marker, suggesting that a low-affinity or noncognate TCR/MHC interaction may be required for initial CD5 up-regulation to intermediate levels. Collectively, these observations favor a maturational process in positive selection in which CD5 up-regulation precedes CD45 and TCR up-regulation.
Molecular cloning of a cDNA clone encoding a phosphoprotein component related to the Ig receptor-mediated signal transduction.
Authors: Inui S , Kuwahara K , Mizutani J , Maeda K , Kawai T , Nakayasu H , Sakaguchi N 
Published: December 2022

Abstract
We have shown previously that a 52-kDa phosphoprotein (p52) co-precipitated with Ig receptor (IgR)-associated MB-1 protein was inducibly phosphorylated by the stimulation with 12-O-tetradecanoyl-phorbol-13-acetate. By immunizing the 52-kDa protein co-precipitated with MB-1, we prepared a mAb (19-14), which can immunoprecipitate the p52 and the associated kinase molecule. Immune complex kinase assay with the 19-14 mAb showed that the p52 is associated with a novel kinase molecule and is involved in IgR-mediated signal transduction. Here we isolated a cDNA clone (alpha 4) from a murine bone marrow cDNA library in lambda gt-11 vector by the 19-14 mAb. The alpha 4 cDNA encodes a novel protein of 340 amino acids with multiple potential phosphorylation sites. The 1.4-kb alpha 4 mRNA is expressed in various cells including cell lines of B lineage, T lineage, monocytic, fibroblast, and normal organs such as liver, spleen, thymus, and brain. To study the molecule encoded by the alpha 4 cDNA, we produced a chimeric protein of the glutathione S transferase (GST)-alpha 4 in pGEX-3X expression vector. The 19-14 mAb binds to the GST-alpha 4 fusion protein. Rabbit anti-alpha 4 Ab prepared by immunizing the GST-alpha 4 fusion protein immunoprecipitated a 52-kDa phosphoprotein from WEHI-231 cells. The 52-kDa phosphoprotein immunoprecipitated by the anti-alpha 4 Ab is tightly associated with kinase activity that is similarly observed with the p52 protein reported previously. Moreover, the 52-kDa phosphoprotein immunoprecipitated with the anti-alpha 4 Ab is identical to the p52 by the protein comparison on non-equilibrium pH gradient gel electrophoresis/SDS-PAGE, isoelectric focusing/SDS-PAGE, and V8 protease mapping. The 52-kDa phosphoprotein is associated with functional components that are inducibly phosphorylated by anti-IgM stimulation. These results suggested that the alpha 4 gene-encoded molecule is functionally involved in the IgR-mediated signal transduction in B cells.
Activation of IFN-alpha, IFN-gamma, MxA, and IFN regulatory factor 1 genes in influenza A virus-infected human peripheral blood mononuclear cells.
Authors: Ronni T , Sareneva T , Pirhonen J , Julkunen I 
Published: December 2022

Abstract
Mononuclear blood cells have an important role in immunity as they produce different cytokines in response to microbial infections. We infected primary human mononuclear blood cells with a pathogenic influenza A virus (A/Beijing/353/89) and studied the activation of IFN-alpha, IFN-gamma, IRF-1, and MxA genes. IFN-alpha and IFN-gamma steady state mRNA levels peaked at 6 to 9 h after infection and declined rapidly thereafter. Only a modest (twofold) increase in IRF-1 mRNA was seen. MxA gene expression, normally strictly regulated by IFN-alpha/beta, had expression kinetics similar to those of IFN mRNA. Infection experiments done in the presence of cycloheximide showed that influenza virus infection could induce all genes studied in the absence of detectable protein synthesis. Pretreatment with IFN-alpha, but not with IFN-gamma, caused a dose-dependent inhibition of influenza virus replication in PBMC, and this inhibition correlated with increasing levels of MxA protein. Influenza virus replication was also inhibited in a stably transfected, MxA-expressing promonocytic U937 cell line. The results suggest that MxA protein significantly contributes to IFN-mediated host defence mechanisms against influenza A virus.
Identification of complement receptor type 1-related proteins on primate erythrocytes.
Authors: Nickells M W , Subramanian V B , Clemenza L , Atkinson J P 
Published: December 2022

Abstract
The purpose of this study was to characterize the structure and function of the immune adherence receptor (CR1, CD35, C3b/C4b receptor) of primates. Western blotting, immunoprecipitation, ELISA, and affinity chromatography with homologous C3b and C4b were utilized. The major cross-reactive E membrane protein of ten species of primates tested was lower in m.w. than was human CR1 and fell into two size groups of 55 to 75 and 130 to 165 kDa. There was 10- to 100-fold more CR1 per primate E than human E. Five species also expressed lesser quantities of a protein similar in m.w. (approximately 200 kDa) to human CR1. In contrast to E, the major cross-reactive protein on PBMC was similar in size to human CR1. Four species also expressed lesser amounts of a lower m.w. protein on their PBMC of the same M(r) as that found on their E. Affinity chromatography demonstrated that the approximately 200-kDa form, if present, was recovered with a similar efficiency to that of human CR1. Three patterns of binding, however, were identified among the lower m.w. proteins: 1) C3b &gt; or = C4b; 2) C4b &gt; C3b; and C3b only or predominantly. The fact that these E proteins cross-react with Ab to human CR1, bind homologous C3b and, in most cases, C4b, and for some species represent the only such protein expressed on their E identifies them as immune adherence receptors. The 70-kDa CR1 of the chimpanzee E seems to arise by alternative splicing of the mRNA encoding the 200-kDa protein. These data raise interesting questions relative to the evolution of CR1 in primates and provide a basis for analysis of structure-function relationships among these size forms of CR1.