bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tissue immunogenicity: the role of MHC antigen and the lymphocyte costimulator B7-1.
Authors: Coulombe M , Yang H , Guerder S , Flavell R A , Lafferty K J , Gill R G 
Published: December 2022

Abstract
Pancreatic islet transplantation represents a potential treatment for insulin-dependent diabetes mellitus. One approach to circumvent the requirement for recipient immune suppression is to reduce or eliminate the immunogenicity of the donor graft prior to transplantation. In this study, we have examined the relative contributions of graft MHC Ag expression and donor-derived costimulatory (CoS) activity to the rejection of islet allografts. Depletion of donor hemopoietic APCs from islet tissue facilitated long-term allograft survival even when donor class I MHC Ag expression was greatly increased by IFN-gamma treatment prior to grafting. Conversely, islet allografts from transgenic mice expressing the CoS molecule B7-1 (CD80) on islet beta cells were acutely rejected even when hemopoietic APCs were eliminated. Thus, B7-1 is sufficient to confer the capacity of islet parenchymal cells to stimulate allorejection. Taken together, these results point towards donor-derived CoS activity as a primary target of intervention therapy to modulate tissue immunogenicity.
IL-2 and TNF receptors as targets of regulatory T-T interactions: isolation and characterization of cytokine receptor-reactive T cell lines in the Lewis rat.
Authors: Mor F , Reizis B , Cohen I R , Steinman L 
Published: December 2022

Abstract
T cells are considered to be of prime importance in immune regulation of both B and T cell functions. The targets of recognition in T-T cell interactions are not clear. Most recent experimental work has focused on the idiotypic regulatory interactions mediated by TCR peptides. There is experimental evidence that regulatory cells exist that do not recognize the TCR. This type of regulation is selectively induced by activated T cells. Therefore, we designed this study to examine the possible role of cytokine receptors as targets of immune regulation. We tested two peptides of IL-2R alpha-chain, 2 of IL-2R beta-chain, and one of TNFR (p60). All peptides were found to be immunogenic at inducing T cell proliferation and four induced Abs in Lewis rats. We generated T cell lines to these five peptides, and tested them both in vitro and in vivo. We found that the T cells exhibited a proliferative response when cultured with activated, irradiated stimulator cells that were augmented upon addition of the cytokine receptor peptide. The cytokine profile of the lines was characterized as well as the Vbeta gene composition. One of the lines significantly protected against active encephalomyelitis. These results point at cytokine receptors as possible targets of immune regulation and T-T cell interactions.
Antigen-dependent regulation of IgE antibody production by human antigen-specific B cells.
Authors: Oshiba A , Gelfand E W 
Published: December 2022

Abstract
Ag-specific B cells from the peripheral blood of immunized donors were separated following rosette formation with tetanus toxin (TT)-coupled immunobeads to study the regulation of T cell-dependent Ab production. Surface IgM+ (sIgM+) B cells rosetting with TT-coated beads produced anti-TT IgM, IgG, and IgE Abs in cultures stimulated with EBV or anti-CD40 Ab in the presence of IL-4; this was associated with increased numbers of B cells positive for sIgG and sIgE. TT-binding sIgM+ B cells also produced significant amounts of anti-TT IgM, IgG, and IgE Abs when they were cultured with autologous T cells in the presence of IL-4. Addition of TT to the IL-4-stimulated, T cell-dependent cultures resulted in higher levels of TT-specific IgM and IgG Abs than observed with T cells alone, but the inclusion of TT with T cells suppressed anti-TT IgE production. Addition of TT Ag to cultures with allogeneic T cells failed to enhance IgM and IgG responses, and the inhibition of IgE production was reduced compared with cultures containing autologous T cells in the presence of Ag. These results demonstrate that the presence of Ag contributes to the regulation of Ab production, resulting in enhanced IgM and IgG responses, but down-regulation of IgE Ab production.
Disregulated expression of CD43 (leukosialin, sialophorin) in the B cell lineage leads to immunodeficiency.
Authors: Ostberg J R , Dragone L L , Driskell T , Moynihan J A , Phipps R , Barth R K , Frelinger J G 
Published: December 2022

Abstract
Leukosialin (CD43 or sialophorin) is a cell surface sialoglycoprotein implicated in cell adhesion and proliferation whose tightly regulated expression in B lymphocytes is likely important for their normal development and/or function. To examine the physiologic role of mouse CD43 (mCD43) in vivo, we exploited transgenic (TG) mice whose developmental expression of mCD43 was extended during B cell differentiation so that mCD43 was now expressed on peripheral B cells. Despite having increased B cells, localization of lymphocytes in the TG spleens appeared normal by immunocytochemistry with anti-CD4, anti-CD8, and anti-B220 mAbs. However, the numbers of splenic germinal centers and the resting sera Ig levels were decreased in the TG mice compared with littermate controls. TG mice had decreased humoral responses to the T-dependent Ags keyhole limpet hemocyanin and OVA, as well as reduced Ag-specific B cell numbers. In contrast, in vitro LPS stimulation of purified TG or control B cells resulted in similar proliferation and IgM responses. Thus, the alteration of B cell mCD43 expression that resulted in profound immunodeficiency in vivo was not due to absolute defects in B cell development or Ab production. However, TG B cells had a decreased ability to homotypically aggregate and to present Ag to the T cell hybridoma B3Z. These data suggest that the immunodeficiency seen in vivo is due to the anti-adhesive forces of mCD43 preventing normal T-B cell interaction. This likely reflects a general property of mucins in regulating cell interactions.
Molecular cloning of guinea pig membrane cofactor protein: preferential expression in testis.
Authors: Hosokawa M , Nonaka M , Okada N , Nonaka M , Okada H 
Published: December 2022

Abstract
Human membrane cofactor protein (MCP) is a widely distributed cell-associated complement-regulatory protein, and recent findings suggest that MCP may be involved in sperm-egg interaction. We have isolated four cDNA clones and one reverse transcriptase-PCR product homologous to human MCP from guinea pig testis. These clones defined five isoform classes generated from a single copy gene by alternative splicing. Reverse transcriptase-PCR revealed that two classes for the clones termed GMP1 and GM2 were predominant. GMP1 consisted of four short consensus repeats (SCRs), regions corresponding to the human serine/threonine/proline-rich C (STP(C)) domain and a human region of unknown significance, a hydrophobic region presumed to be a transmembrane domain, and a cytoplasmic region. Identity with human MCP in the SCR region was 56% at the amino acid level and 71% at the nucleotide level. GM2 had the same structure as GMP1, except that it lacked the fourth SCR, which is presumed to be essential for C3b binding of human MCP. Northern blotting analysis of various tissues revealed a significant level of MCP transcripts in testis. Guinea pig MCP is likely to have only one STP domain that is homologous to human STP(C) and is similar in this respect to human spermatozoa MCP. Gene analysis revealed a single base deletion and a lack of consensus sequences for splicing in the guinea pig regions corresponding to human STP(A) and STP(B), respectively. These results suggest that guinea pig MCP plays a more restricted role in reproduction than does human MCP.
Molecular cloning of a novel protein antigen of Leishmania major that elicits a potent immune response in experimental murine leishmaniasis.
Authors: Webb J R , Kaufmann D , Campos-Neto A , Reed S G 
Published: December 2022

Abstract
BALB/c mice are highly susceptible to infection with the protozoan parasite Leishmania major. This susceptibility has been attributed, in part, to the expansion of parasite-specific CD4+ Th2 cells that antagonize Th1 responses and promote humoral immunity. In the present study, we have utilized sera from L. major-infected BALB/c mice to screen an L. major amastigote cDNA expression library. One of the clones detected encodes a novel Ag designated as L. major stress-inducible 1 (LmSTI1). LmSTI1 contains six copies of the tetratricopeptide consensus motif and is highly related to a family of stress-inducible proteins that is conserved from yeast to humans. Sera from L. major-infected BALB/c mice have LmSTI1-specific Ab titers in excess of 1:200,000, comprised predominantly of IgG1, IgG2A, and IgG2B isotypes. Recombinant LmSTI1 protein elicited strong proliferative responses from draining lymph node cells of L. major-infected BALB/c mice at both early (10 days) and late (28 days) stages of infection and elicited production of high levels of IFN-gamma and low levels of IL-4. In contrast, soluble leishmanial lysate elicited high levels of IL-4 and low IFN-gamma production. Thus, we have identified an Ag of Leishmania capable of eliciting a mixed cellular response that is skewed toward a Th1 phenotype in susceptible BALB/c mice with advanced infections. In addition, analyses of sera from human patients with cutaneous, visceral, and post-kala azar visceral leishmaniasis indicated that a majority of individuals from all three clinical groups mounted strong humoral responses against LmSTI1.
Functions of domain 1 and 4 of vascular cell adhesion molecule-1 in alpha4 integrin-dependent adhesion under static and flow conditions are differentially regulated.
Authors: Abe Y , Ballantyne C M , Smith C W 
Published: December 2022

Abstract
To assess the potential contributions of endothelial vascular cell adhesion molecule-1 (VCAM-1) to leukocyte adhesion under conditions of flow, we evaluated the effects of cytokine stimulation of HUVEC on primary capture, rolling, and stable adhesion of mono- and lymphoblastoid cells in a parallel-plate flow chamber. Stimulation of HUVEC with IL-1beta or IL-4 for 24 h induced surface expression of VCAM-1, consistent with published results. Using blocking mAbs to inhibit specific adhesion molecules, we found that a significant level of primary capture at wall shear stresses between 0.5 and 2.0 dynes/cm2 could be attributed to alpha4 integrin and VCAM-1. This primary adhesion under flow was most often characterized by abrupt stationary adhesion with little evidence of rolling. Studies with IL-1beta-stimulated HUVEC revealed that domain 1 of VCAM-1 was solely responsible for alpha4 integrin-dependent primary capture under flow, but both domains 1 and 4 were utilized in alpha4 integrin-dependent adhesion under static conditions. In contrast to results obtained with these cytokines alone, stimulation of HUVEC with a combination of IL-1beta and IL-4 markedly reduced alpha4/VCAM-1-dependent adhesion under flow, even though the surface levels of VCAM-1 were greater than with either cytokine alone, and alpha4/VCAM-1-dependent adhesion under static conditions was intact. These results demonstrate that distinct functional differences exist between the interactions of VCAM-1 and alpha4 integrin under static and flow conditions, and they reveal the potential for endothelial modulation of adhesion under flow without altering VCAM-1-dependent adhesion under static conditions.
Critical role of Lyn kinase in inhibition of neutrophil apoptosis by granulocyte-macrophage colony-stimulating factor.
Authors: Wei S , Liu J H , Epling-Burnette P K , Gamero A M , Ussery D , Pearson E W , Elkabani M E , Diaz J I , Djeu J Y 
Published: December 2022

Abstract
The signal pathway for control of apoptosis in human neutrophils is currently unknown. In this study, we provide the first evidence that a Src family tyrosine kinase, Lyn, plays a key role in inhibition polymorphonuclear (PMN) cell death. Several nuclear proteins associated with apoptosis, i.e., p53, cdc2, and Rb, were absent from PMN. Bcl-2, known to inhibit apoptosis, was also not expressed. Programmed cell death that rapidly occurred in PMN could be arrested by granulocyte-macrophage CSF (GM-CSF), but this activation did not induce p53, cdc2, retinoblastoma, or Bcl-2 expression. Instead, GM-CSF produced a rapid activation of Lyn and Hck, but not Fgr, tyrosine phosphorylation within 1 min. Co-immunoprecipitation studies indicated that only Lyn, but not Hck, was physically coupled to GM-CSF receptor. By histologic assessment and evaluation of DNA fragmentation, only antisense Lyn, but not antisense Hck or antisense Fgr, could reverse the cell survival advantage provided by GM-CSF. Therefore, the physical coupling of Lyn to GM-CSF receptor and its early activation are required for inhibition or delay of apoptosis in PMN.
Thymic expression of myelin basic protein (MBP). Activation of MBP-specific T cells by thymic cells in the absence of exogenous MBP.
Authors: Fritz R B , Zhao M L 
Published: December 2022

Abstract
Previous studies have shown golli-myelin basic protein (MBP) mRNA to be expressed in the thymus of normal SJL mice, but translation of the mRNA was not assessed. To test for the presence of immunoreactive protein, single cell suspensions were prepared from adult SJL thymus and cultured with syngeneic MBP-specific T cells. After 48 h [3H]thymidine was added to the microcultures to assess T cell proliferation. MBP-specific T cell lines proliferated strongly (stimulation index range, 13-31). T cell lines specific for MBP exon 2, MBP peptide 89-101, proteolipid protein peptide 139-151, and OVA gave stimulation indices of 10-13, 5-6, 2-3, and 2-3, respectively. Stimulatory activity could be abrogated by irradiation of either the thymic cells or the MBP-specific T cells. Stimulatory activity was a property of a minor population of plastic-adherent thymic cells. Monoclonal anti-I-As Ab added to the microcultures inhibited the reaction by 77%. MBP-specific T cells cultured with syngeneic nonirradiated thymus cells in the absence of added MBP transferred experimental autoimmune encephalomyelitis adoptively to syngeneic recipients. These findings indicate that golli-MBP mRNA is translated in normal SJL thymus, and that peptides reactive with MBP-specific T cells in the context of class II MHC molecules are expressed.
Induction of anergy in CD8 T cells by B cell presentation of antigen.
Authors: Höllsberg P , Batra V , Dressel A , Hafler D A 
Published: December 2022

Abstract
Induction of T cell anergy is thought to occur during activation in the absence of adequate costimulation. Here we demonstrate induction of anergy in a CD8 T cell clone by its cognate Ag in the presence of B7-1 and B7-2 costimulation. Primary activation of a CD28+CD8+ T cell clone by either human T cell lymphotrophic virus type I (HTLV-I) Tax11-19 peptide-pulsed EBV-transformed B cells, CD40L-stimulated B cells, or T cells was sufficient to induce complete unresponsiveness to a secondary Ag challenge. This was not caused by lack of B7 costimulation since the APCs expressed B7-1 and B7-2 and failed to induce anergy in an MBP peptide 84-102-reactive CD4 T cell clone. While anergic CD8 T cells did not proliferate, they retained their ability to lyse peptide-pulsed target cells. However, Ag stimulation failed to induce IL-2 mRNA transcription and IL-2 secretion, although immediate early tyrosine phosphorylation was normal and anti-CD3 cross-linking induced identical levels of CD40L expression in anergized and non-anergized CD8 T cells. Secondary Ag stimulation in the presence of exogenous IL-2, however, resulted in normal proliferative response. Moreover, while stimulation of CD8 T cells with PHA and B cells induced anergy, CD8 T cell stimulation with PHA and mononuclear cells failed to do so. In addition, the presence of mononuclear cells during the exposure of CD8 T cells to peptide-pulsed B cells prevented the induction of anergy. Together, our observations demonstrate that at least a subpopulation of CD8 T cells are anergized when costimulation is provided by B cells or T cells.
Preferential involvement of Go and Gz proteins in mediating rat natural killer cell lysis of allogeneic and tumor target cells.
Authors: Maghazachi A A , Al-Aoukaty A , Naper C , Torgersen K M , Rolstad B 
Published: December 2022

Abstract
IL-2-activated NK cells from PVG rats potently lyse target cells expressing allo-MHC class I determinants. Here, we investigated the role that G proteins play in mediating this activity. Pretreatment of NK cells with pertussis toxin (PT) or cholera toxin (CT) inhibited NK cell killing of tumor (YAC-1 or P815), and allogeneic target cells. ADP ribosylation assay revealed that PT ADP ribosylates a 39-kDa G protein, whereas CT ADP ribosylates a 45 to 47-kDa G protein in PVG NK cell membranes. Membranes prepared from intoxicated NK cells with either PT or CT lost their ability to incorporate [32P]NAD. These membranes possess Gi, Go, Gs, and Gz as demonstrated by immunoblot analysis. However, Gq was not clearly detected by this method. IL-2-activated NK cells were permeabilized with streptolysin O. Permeabilized cells incorporated Abs to Gi, Go, Gz, Gs, and Gq as determined by flow cytometric analysis. When Abs to Go or Gz, but not to Gi, Gs, or Gq, were incorporated inside permeabilized NK cells, a significant reduction in the lysis of tumor or allo-MHC target cells was observed, suggesting that Go and Gz play important roles in transducing the signals necessary to lyse target cells. Our results show for the first time a role for G proteins in mediating NK cell killing of allo-MHC-encoded target cells, and provide evidence for Gz protein involvement in NK cell recognition of target cells. The effect of Gz is novel and has not been previously described in any other system or cell type.
Biochemical and serologic evidence for the existence of functionally distinct forms of the CD94 NK cell receptor.
Authors: Pérez-Villar J J , Carretero M , Navarro F , Melero I , Rodríguez A , Bottino C , Moretta A , López-Botet M 
Published: December 2022

Abstract
The CD94 NK cell receptor is assembled as a disulfide-linked dimer and appears to be encoded by a single-copy gene of the C-type lectin superfamily. In reverse Ab-dependent cellular cytotoxicity assays, CD94-specific mAbs may either trigger or inhibit cytotoxicity in distinct subsets of NK clones, termed groups A and B, respectively. The molecular basis for this functional ambivalence of CD94 has been addressed. CD94 molecules immunoprecipitated with the HP-3B1 mAb from the two different subsets of NK clones were comparatively analyzed by SDS-PAGE. Under reducing conditions, the stimulating form of CD94 from group A clones displayed a significantly lower Mr (39 kDa) than the inhibitory form of group B clones (Mr = 43 kDa). Analyses of N-glycanase and V8 protease-digested samples indicated that the two CD94 forms are homologous. A CD94-specific mAb (Z199) that did not recognize cells transfected with a CD94 cDNA (LL288) was characterized. Z199 did not bind to group A clones, whereas its reactivity with group B NK cells was indistinguishable from that of other CD94-specific mAbs. Different from the HP-3B1 mAb, the Z199 mAb displayed only inhibitory effects in reverse Ab-dependent cellular cytotoxicity assays. Immunoprecipitation studies confirmed that Z199 selectively identified the 43-kDa CD94. Our study proves the existence of at least two biochemically and serologically distinct CD94 molecules, whose selective/predominant expression at the clonal level correlates with the pattern of response (i.e., inhibition vs activation) of NK cells to ligation by CD94-specific mAbs.
Rapid immune activation by CpG motifs in bacterial DNA. Systemic induction of IL-6 transcription through an antioxidant-sensitive pathway.
Authors: Yi A K , Klinman D M , Martin T L , Matson S , Krieg A M 
Published: December 2022

Abstract
Unmethylated CpG dinucleotides (CpG motif) in bacterial DNA or synthetic oligodeoxynucleotides (CpG DNA) rapidly activate murine B cells to secrete IL-6 and IgM, as well as to proliferate. Within 30 min after CpG DNA stimulation in vivo, IL-6 mRNA levels were increased in liver, spleen, and thymus cells. Serum IL-6 protein was markedly increased within 1 h of stimulation. Treatment of a B cell line with CpG DNA led to an increase in the transcriptional activity of the IL-6 promoter. This CpG DNA-induced IL-6 production was not mediated via either a protein kinase C (PKC)-, protein kinase A (PKA)-, or nitric oxide (NO.)-dependent pathway but was inhibited by an antioxidant. In addition, the level of intracellular reactive oxygen species was increased within 20 min after CpG DNA, but not control non-CpG DNA, treatment. These results suggest that CpG DNA-induced IL-6 production is mediated through a reactive oxygen intermediate-dependent pathway. CpG DNA-mediated IL-6 production was enhanced by simultaneous signals delivered through the Ag receptor. The addition of neutralizing Abs against IL-6 to B cell cultures along with CpG oligodeoxynucleotides essentially abolished the CpG DNA-induced increased IgM secretion but had no significant effect on the B cell proliferation induced by the CpG motif. Our results suggest that the induction of IL-6 expression in response to CpG motifs in bacterial DNA may be an important immune defense mechanism that facilitates a rapid response to microbial infection.
Identification of the rhesus monkey HLA-G ortholog. Mamu-G is a pseudogene.
Authors: Boyson J E , Iwanaga K K , Golos T G , Watkins D I 
Published: December 2022

Abstract
HLA-G is a nonclassical MHC class I molecule that is primarily expressed in the placenta. To investigate whether rhesus monkeys possess an HLA-G ortholog, we cloned and sequenced MHC class I cDNAs from the rhesus placenta. We identified two rhesus MHC class I cDNAs with sequence similarity to HLA-G. Each cDNA contained premature stop codons and frameshift mutations, suggesting that it was derived from an MHC class I pseudogene. Gene trees constructed using MHC class I alleles from human and nonhuman primates revealed that the rhesus placental pseudogene alleles clustered with HLA-G orthologs from the human, chimpanzee, and gorilla. These data suggested that this rhesus MHC class I pseudogene is an HLA-G ortholog. This locus was, therefore, designated Mamu (Macaca mulatta)-G. PCR amplification of a portion of Mamu-G from the genomic DNA of five rhesus monkeys resulted in the identification of five additional Mamu-G alleles and revealed the presence of four Mamu-G alleles in one rhesus monkey, suggesting that Mamu-G had been duplicated in this individual. Furthermore, the analysis of 81 MHC class I clones isolated from a rhesus placenta cDNA library did not result in the isolation of Mamu-G cDNAs, nor the isolation of any additional HLA-G homologs, suggesting that Mamu-G was transcribed at negligible levels. Given the similarity of rhesus monkey and human placenta structure and function, these data raise interesting questions regarding the role of HLA-G in pregnancy.