bluuebunny/crossref_metadata_2025_split huggingface dataset:
Candidacidal mechanisms in the human neonate. Impaired IFN-gamma activation of macrophages in newborn infants.
Authors: Maródi L , Káposzta R , Campbell D E , Polin R A , Csongor J , Johnston R B 
Published: December 2022

Abstract
We studied the interaction between Candida albicans and mononuclear phagocytes derived from cord blood. In the presence of normal serum, the extent of phagocytosis and killing of candida by monocyte-derived macrophages was equivalent for newborns and adults. In the absence of serum both phagocytosis and killing by macrophages were reduced by half, but cord and adult cells were still equivalent. Mannosylated BSA and mannan inhibited ingestion of unopsonized candida by macrophages, suggesting a role for the mannose receptor. Exposure of cord and adult macrophages to IFN-gamma (10-500 U/ml) gave quantitatively different results in Candida killing, as well as in release of superoxide anion (O2-). Maximal increase in these functions with adult macrophages was achieved with 100 U/ml IFN-gamma. No enhancement with cord macrophages could be detected after treatment with 100 U/ml, and at 500 U/ml there was still significantly lower killing and O2- release compared with adult cells. Defective up-regulation of O2- release was also present in cord monocytes exposed to IFN-gamma on day 0. Studies of the surface expression of IFN-gamma receptors using a "nonblocking" mAb against the IFN-gamma receptor revealed a comparable number of receptors on cord and adult monocytes. When blocking Abs were used, however, there was a three times higher number of positive cells in cord monocytes. Specific binding of 125I-IFN-gamma to cord monocytes and macrophages was also higher compared with adult cells. These data suggest that neonatal macrophages have a normal capacity to ingest and kill both opsonized and unopsonized Candida but cannot be fully activated by IFN-gamma, a finding that could not be attributed to lower expression of IFN-gamma receptors on the neonatal cells.
Transfection of vitamin D receptor cDNA into the monoblastoid cell line U937. The role of vitamin D3 in homotypic macrophage adhesion.
Authors: Hewison M , Dabrowski M , Faulkner L , Hughson E , Vadher S , Rut A , Brickell P M , O'Riordan J L , Katz D R 
Published: December 2022

Abstract
A 2-kB cDNA for the vitamin D receptor (VDR) was cloned in sense orientation into the plasmid pMEP4 (containing a cadmium-inducible metallothionein II promoter and a hygromycin-resistance selection gene) and transfected into monoblastoid U937 cells. The resultant cell line, DH39, expressed two species of VDR mRNA: 4.6-kb wild-type mRNA (present in native U937 cells or cells transfected with pMEP4 alone) and 2-kb transfected mRNA, which increased with cadmium treatment. Binding studies (using the active vitamin D metabolite, 1,25-dihydroxycholecalciferol (1,25-DHCC)) showed that DH39 cells contained five times more VDR per cell than controls, and ten times more after cadmium treatment. DH39 were sensitive to 1,25-DHCC: adding cadmium with 100 nM 1,25-DHCC for 72 h completely inhibited proliferation and induced concomitant differentiation. Unlike control cells, differentiation of DH39 by 1,25-DHCC led to homotypic cell-cell adhesion and formation of macrophage clusters. FACS analysis showed that 1,25-DHCC increased the number of cells expressing CD11b in both DH39 and controls, and the number of cells expressing CD11c in DH39. There was a quantitative increase in mean fluorescence intensity of expression of CD11a and CD18 in DH39. Northern blotting showed increased CD11a and CD18 mRNA in DH39. Ab inhibition of 1,25-DHCC-induced homotypic adhesion showed that CD11a/18 mediated the cell-cell clustering. CD50 expression was decreased on DH39, but the CD11a/18 ligand implicated was CD54. DH39 provides a model system not only for investigating the VDR role in 1,25-DHCC anti-proliferative effects, but also for regulation of homotypic macrophage adhesion mechanisms that are important in disease pathogenesis.
Lipopolysaccharide induces activation of the Raf-1/MAP kinase pathway. A putative role for Raf-1 in the induction of the IL-1 beta and the TNF-alpha genes.
Authors: Reimann T , Büscher D , Hipskind R A , Krautwald S , Lohmann-Matthes M L , Baccarini M 
Published: December 2022

Abstract
Bacterial LPS is a potent macrophage activator. The early steps in LPS signal transduction involve the tyrosine phosphorylation and activation of a number of kinases of the src family, and inhibition of this pathway causes a severe impairment in the production of the cytokines TNF-alpha and IL-1 beta. We find that LPS-induced macrophages activation also involves the Raf-1 kinase, a key component in mitogenic signal transduction. Treatment of BAC-1.2F5 macrophages with LPS causes phosphorylation and activation of Raf-1. This is paralleled by the stimulation of MEK-1 and MAP-kinase activity and by the phosphorylation of the transcription factor Elk-1, a nuclear target of MAP-kinase. Activation of the Raf/MAP-kinase pathway was inhibited upon pretreatment of the cells with genistein, a tyrosine kinase inhibitor. Raf-1 must thus lie downstream of tyrosine kinase in LPS signal transduction. However, Raf-1 is not a direct substrate of a LPS-induced tyrosine kinase, because Raf-1 immunoisolated from LPS-induced cells contains only phosphoserine. This resembles the situation after CSF-1-stimulation of macrophages, in which Raf-1 clearly transduces a signal generated by the CSF-1 receptor kinase, but is phosphorylated exclusively in serine. Phosphopeptide maps of Raf-1 immunoprecipitated from LPS- or CSF-1-treated cells are indistinguishable, suggesting that these agents activate Raf-1 by similar mechanisms. Finally, v-raf-infected BAC-1.2F5 macrophages were found to constitutively express low levels of IL-1 beta and TNF-alpha. These data argue that Raf-1 functions downstream of tyrosine kinases in LPS-mediated macrophage activation and cytokine production.
Immunosuppression to cardiac allografts and soluble antigens by anti-vascular cellular adhesion molecule-1 and anti-very late antigen-4 monoclonal antibodies.
Authors: Isobe M , Suzuki J , Yagita H , Okumura K , Yamazaki S , Nagai R , Yazaki Y , Sekiguchi M 
Published: December 2022

Abstract
Effective activation of T cells in immune responses depends on two signals, one from the CD3/TCR complex and another from accessory cell surface proteins. Very late Ag-4 (VLA-4) can exert a costimulatory function upon binding with vascular cellular adhesion molecule-1 (VCAM-1). We investigated the effects of mAbs against VCAM-1 and VLA-4 on cardiac allograft survival and humoral response to soluble Ags. BALB/c hearts were transplanted into C3H/He recipients. mAbs (100 micrograms/day) were administered i.p. for the first 6 days. Graft survival in mice treated with M/K-2 (anti-VCAM-1; median survival: 20 days, n = 6) and those treated with PS/2 (anti-VLA-4; 30 days, n = 6) was greater than that in control mice (8 days, n = 7). Eight of 18 mice treated with both M/K-2 and PS/2 accepted the grafts over 65 days, and five of them accepted the grafts over 100 days. Allografts treated with the two mAbs showed scattered infiltration of leukocytes without evidence of active rejection at 65 days. Mice with long-surviving cardiac grafts were challenged with skin grafts from donor and third-party (C57BL/6) strains. Survival of the donor-type skin was significantly greater than that of the third-party skin. One mouse specifically accepted the donor-type skin indefinitely (&gt; 150 days). FACS analysis of splenocytes at 55 days after transplantation showed complete recovery of VLA-4 expression from a down-regulation observed at day 7. In addition, mice immunized with heat-aggregated human gamma-globulin did not produce specific Ab, even after boost immunization, if PS/2 was administered at the time of the first immunization. This unresponsiveness to xenogeneic protein lasted for more than 50 days. These results indicate that in vivo administration of anti-VCAM-1 and anti-VLA-4 mAbs induces specific immunosuppression to cardiac allografts and soluble Ags.
Defective T cells from gld mice play a pivotal role in development of Thy-1.2+B220+ cells and autoimmunity.
Authors: Yasutomo K , Maeda K , Nagata S , Nagasawa H , Okada K , Good R A , Kuroda Y , Himeno K 
Published: December 2022

Abstract
The gld mouse represents a fascinating animal model of autoimmune disease, which is characterized by massive development of Thy-1.2+B220+ CD4-CD8- cells. These cells thus have double positive markers for T and B cells, but are double negative for CD4 and CD8 markers and are thus designated DN cells in the present context. An additional important feature in gld mice is a defect in expression of Fas ligand. To investigate the regulatory role of bone marrow-derived cells for the development of these DN cells and of gld autoimmunity, we constructed chimeric mice transplanted with fetal liver cells or fetal thymus from gld mice into nonirradiated severe combined immunodeficient (SCID) mice. These chimeric mice regenerated, developed both these DN cells and the gld autoimmune syndrome and also generalized lymphoproliferative disorders. However, when fetal liver cells from both gld and non-gld mice (C57BL/10 Thy-1.1 mice) were co-transplanted into SCID mice, the development of DN cells was apparently inhibited. Further, this inhibition was also seen in SCID mice that had been grafted with both gld and non-gld fetal thymus revealing the pivotal role played by T cells in development of DN cells. When B cells purified from non-gld (C3H+/+) mice were transplanted into SCID mice grafted with gld fetal thymus, the development of DN cells was not inhibited. Taken together, these findings indicate that T cells from non-gld mice inhibit the expression of gld features, e.g., lymphoproliferation, immune-based nephritic disease, and autoantibody production. These findings also suggest that the Fas ligand is selectively expressed on T cells.
Expression and function of the MAdCAM-1 receptor, integrin alpha 4 beta 7, on human leukocytes.
Authors: Erle D J , Briskin M J , Butcher E C , Garcia-Pardo A , Lazarovits A I , Tidswell M 
Published: December 2022

Abstract
Recirculation of mouse lymphocytes to the gut involves binding of the lymphocyte integrin alpha 4 beta 7 to the mucosal vascular addressin, MAdCAM-1. In humans, indirect evidence suggests that CD4+ T cells that express high levels of alpha 4 beta 7 migrate selectively to the gut. We now report that human adult blood CD8+ T cells and B cells, like CD4+ T cells, have heterogeneous expression of alpha 4 beta 7. In contrast, NK cells, eosinophils, and newborn blood T and B cells have relatively homogeneous expression of alpha 4 beta 7. CD4+ and CD8+ T cell expression of alpha 4 beta 7 was related to age, CD45RA expression, and integrin beta 1 (CD29) expression, suggesting that alpha 4 beta 7 expression changes after primary activation of CD4+ and CD8+ T cells in vivo. To directly determine whether human alpha 4 beta 7 mediates adhesion to MAdCAM-1, we performed in vitro adhesion assays with two alpha 4 beta 7+ human lymphoma cell lines. The results indicate that human alpha 4 beta 7 is a receptor for MAdCAM-1, whereas alpha 4 beta 1 is not. Adhesion of HUT 78 cells to MAdCAM-1 required Mn2+, whereas adhesion of RPMI 8866 cells did not, suggesting that alpha 4 beta 7 may have at least two distinct functional states. The ability of lymphocytes to bind to MAdCAM-1 and recirculate to mucosal organs is likely to be influenced both by the level of alpha 4 beta 7 expression and by the functional state of the alpha 4 beta 7 molecule.
Induction of T cell differentiation and lymphomagenesis in the thymus of mice with severe combined immune deficiency (SCID).
Authors: Murphy W J , Durum S K , Anver M R , Ferris D K , McVicar D W , O'Shea J J , Ruscetti S K , Smith M R , Young H A , Longo D L 
Published: December 2022

Abstract
Severe combined immune deficiency (SCID) mice have a defect in their recombinase system and cannot productively rearrange their immune receptor genes. Thus, SCID thymocytes are arrested at the immature "triple negative" phase, not expressing CD3, CD4, or CD8 surface markers. Whole body irradiation of SCID mice induced maturation of their thymocytes to the CD4+/CD8+ double positive, CD3+low stage of differentiation, and resulted in the generation of a thymic cortical region on histologic examination. No mature single positive T cells were detected in the thymus or the periphery. VDJ rearrangements of TCR-beta with restricted clonality were observed in the double positive cells from a given individual. The CD3 complex was expressed on some of these cells, but the cells failed to mobilize intracellular calcium after cross-linking with CD3 Abs. The double positive cells appeared several weeks after irradiation, persisted for many months in the thymus, and by 6 mo generally developed into metastatic lymphoma. Retroviral activation was undetectable in both the preneoplastic and transformed thymocytes. Thus, it appears that the earliest steps in T cell development can be induced in SCID mice by inducing DNA breaks with radiation. This system represents a model of early thymic development, preneoplasia, and neoplasia.
Inhibition of T cell activation by a monoclonal antibody reactive against the alpha 3 domain of human MHC class I molecules.
Authors: Smith D M , Bluestone J A , Jeyarajah D R , Newberg M H , Engelhard V H , Thistlethwaite J R , Woodle E S 
Published: December 2022

Abstract
A long term goal of investigators working in our laboratory has been to develop new mAbs for use as immunosuppressive agents. As a means toward achieving this goal, several new mAbs (hybridomas) have been developed by screening fusions for supernatants that possess T cell-inhibitory properties. Of these new mAbs, one mAb, designated 5H7, has been shown to possess both a unique combination of specificity for a monomorphic determinant of the alpha 3 domain of human class I MHC heavy chains and highly potent T cell inhibitory properties. mAb 5H7 profoundly inhibited T cell proliferation in response to anti-CD3 mAb in primary or secondary allogenic MLR or in primary human anti-mouse xenogenic MLR. mAb 5H7 inhibited expression of an early T cell activation marker, Leu23 (CD69); expression of IL-2Rs; and IL-2 production by both CD4+ and CD8+ T cells. mAb 5H7 inhibited IL-2 release by the Jurkat (E6-1) human T cell leukemia line in response to immobilized anti-CD3 mAb, thus, providing further evidence that 5H7 can inhibit activation directly at the level of the T cell. 5H7 profoundly blocked CD3-dependent (anti-CD3, anti-CD3 plus PMA, or anti-CD3 plus anti-CD28) pathways, but only partially blocked a CD3-independent (anti-CD28 plus PMA) pathway of T cell activation. In conclusion, class I MHC molecules that are expressed on the T cell may regulate early TCR/CD3-dependent signaling events. In addition, 5H7 mAb may provide a reagent for suppression of cellular immunity in vivo.
Structure-immunogenicity relationship of melittin, its transposed analogues, and D-melittin.
Authors: King T P , Wade D , Coscia M R , Mitchell S , Kochoumian L , Merrifield B 
Published: December 2022

Abstract
Melittin, a 26-residue bee venom peptide, is known to induce murine Abs specific for its hydrophilic C-terminus of residues 20-26 and T cell responses specific for its hydrophobic mid-region of residue 11-19. Synthetic melittin analogues with transposed sequences of Ac(21-26) (1-20) and Ac(26-21) (1-20) are found to induce murine Abs specific for the transposed peptide segment and to induce T cell responses that are cross-reactive with melittin. Compared with melittin, the transposed melittin analogues are weaker immunogens and have lower hemolytic activities, lower helical contents, and a lower degree of association in micelles. A melittin analogue with a lactoside group at its C-terminus was found to induce lactoside-specific murine Abs. Present studies show that another analogue with a lactoside group at its N-terminus induces only Abs specific for the C-terminal region of melittin, and no lactoside-specific Abs are detected. These immunochemical observations suggest that the immunogenicity of melittin or its analogues is a consequence of its binding to cell membranes with subsequent oligomer formation in lipid bilayers. Apparently melittin or its analogues bind to cell membrane in an asymmetric manner with the exposed and the buried segments functioning as B and T cell epitopes, respectively. D-melittin is non-immunogenic in mice, although D-melittin has the same hemolytic activity as melittin. This finding may be correlated with the known resistance of D-melittin to proteolysis and hence to processing for Ag presentation to T lymphocytes.
Kappa light chain rearrangement in mouse fetal liver.
Authors: Ramsden D A , Paige C J , Wu G E 
Published: December 2022

Abstract
Ig variable domains are generated by the recombination of V, D, and J segments (V(D)J rearrangement). V(D)J rearrangement is capable of generating a vast repertoire of different variable domains. In this report, we quantify and characterize the repertoire of kappa rearrangements in fetal liver ontogeny. VJ kappa rearrangements are first observable at approximately day 14 of gestation. Characterization of these rearrangements indicates that only 33% are in a productive reading frame, which supports the argument that they have been generated recently and have not as yet undergone significant Ag-driven selection. Further analysis of rearrangements from a pool of 133 cloned VJ kappa junctions (from both day 14 and day 16 of gestation) indicates that the repertoire is fairly diverse with respect to the V kappa gene families used, as well as the number of members from each gene family. The frequency of V kappa 4 family use in rearrangements to J kappa 5, however, was approximately twice that of the frequency of V kappa 4 family use in rearrangement to other J kappa s. The fine structure of fetal VJ kappa junctions was also diverse, which indicates that precise deletion of sequence identities shared between rearranging V kappa J kappa pairs does not significantly reduce junctional diversity, as has been observed in DJH rearrangements. Lastly, a number of junctions contained P nucleotides, in contrast to the repertoire of expressed VJ kappa junctions.
Structure-function studies of anti-3-fucosyllactosamine (Le(x)) and galactosylgloboside antibodies.
Authors: Snyder J G , Dinh Q , Morrison S L , Padlan E A , Mitchell M , Yu-Lee L Y , Marcus D M 
Published: December 2022

Abstract
We are studying murine mAbs against two carbohydrate epitopes, 3-fucosyllactosamine (Le(x), CD15) and galactosylgloboside. The VH domains of both panels of Ab are encoded by VH441, a member of the X24 family of Ig genes. To evaluate the contribution of the heavy chain CDR3 to the affinity of the anti-3-fucosyllactosamine Ab, CDR3-H of PMN6, a low affinity Ab, was replaced by the CDR3 of PM81, a higher affinity Ab. The affinity of the chimeric 6/81 Ab was increased when the heavy chain was paired with the PM81 light chain, but not when paired with another light chain (M5), which differs from PM81 light chain by three amino acids. To evaluate the contribution of somatic mutations to the binding of GalGb4, the 3A9 VH sequence, which contains three amino acid substitutions, was replaced by a germ-line sequence encoded by either VH441 or VHX24. The chimeric Ab, 441/3A9 and X24/3A9, bound Ag as well as the wild-type 3A9 Ab. Computer models of the Fv fragments of PM81 and 3A9 were compared with the crystal structure of the Fv fragment of J539, a galactan-binding myeloma protein that is encoded by the same VH and VK genes as 3A9. The surfaces of 3A9 and J539 have shallow pockets that are potential Ag-binding sites. Replacement of CDR3-H Tyr99, which is a prominent component of the pocket, by Ala abolished the binding of Ag. In contrast, the Fv surface of PM81 contains a large cleft rather than a pocket. These models indicate how the same VH gene segment can be used to encode Abs that exhibit different specificities.
Follicular dendritic cells retain HIV-1 particles on their plasma membrane, but are not productively infected in asymptomatic patients with follicular hyperplasia.
Authors: Schmitz J , van Lunzen J , Tenner-Racz K , Grossschupff G , Racz P , Schmitz H , Dietrich M , Hufert F T 
Published: December 2022

Abstract
During HIV-1 infection, extensive alterations can be observed in the germinal centers (GCs) of lymphatic tissue. The initial hyperplasia of GCs is followed by disintegration and involution of these structures. The process is accompanied by progressive destruction of the network of follicular dendritic cells (FDCs). We investigated whether or not the destruction of GCs is caused by HIV-1 infection of FDCs in vivo. FDCs were purified by FACS or magnetic cell sorter (MACS) from enlarged lymph nodes (LNs) of four asymptomatic HIV-1-infected patients with persistent generalized lymphadenopathy. In situ hybridization demonstrated positive signals for HIV-1 RNA on the cell membrane of FDCs. Virus particles attached to the dendritic network could be demonstrated by electron microscopy, but budding was not seen. Furthermore, proviral DNA was detected by nested PCR (NPCR) in limiting dilution assays of FACS-purified FDCs (up to 1.0 x 10(4) cells) in only one cell fraction. In comparison, proviral DNA could be found in 5.0 x 10(3) to 2.5 x 10(5) FACS-purified Th cells obtained from peripheral blood and in 7.5 x 10(5) to 2.5 x 10(4) Th cells from LN of the same patients. In conclusion, FDCs retain HIV-1 particles on their cell membrane during HIV-1 infection, but the progressive destruction of FDC in vivo is probably not caused by a productive infection of FDCs with HIV-1.
Dual stimulatory and inhibitory effect of NK cell stimulatory factor/IL-12 on human hematopoiesis.
Authors: Bellone G , Trinchieri G 
Published: December 2022

Abstract
NK cell stimulatory factor, or IL-12 (NKSF/IL-12), is a heterodimeric cytokine produced by monocyte-macrophages, B cells, and possibly other accessory cell types. Although the major biologic effects of NKSF/IL-12 have been demonstrated on mature T and NK cells, in which it induces cytokine secretion, increased cytotoxicity, and proliferation, recent evidence in the murine system has suggested that NKSF/IL-12 may play a role in the differentiation of early lymphohematopoietic progenitor cells and thymocytes. In this paper, we have analyzed the effect of human rNKSF/IL-12 on the formation of colonies by highly enriched hematopoietic progenitor cells from human peripheral blood and bone marrow. At concentrations between 1 and 10 ng/ml, NKSF/IL-12 synergizes with a combination of steel factor and IL-3 to induce formation of mixed, erythroid, and myeloid colonies. Therefore, human NKSF/IL-12, like murine NKSF/IL-12, seems to belong to a small group of early acting cytokines, including IL-6, granulocyte-CSF, leukemia-inhibitory factor, and IL-11, which are able to synergize with steel factor and IL-3 to induce proliferation and differentiation of very early hematopoietic progenitor cells. However, in the presence of enriched preparations of NK cells cultured together with the progenitor cells, NKSF/IL-12 inhibits formation of hematopoietic colonies supported by IL-3 and granulocyte-macrophage CSF, by inducing production of IFN-gamma and TNF-alpha, two cytokines with synergistic inhibitory effects on hematopoietic colony formation. Because cell types that are able to produce NKSF/IL-12 are present in normal bone marrow and NKSF/IL-12 production in vivo and can be stimulated during bacterial or parasitic infection, it is possible that the direct stimulatory effect of NKSF/IL-12 on hematopoietic progenitor cells and the indirect inhibitory effect mediated by secondary cytokine production by lymphoid cells may play a role in the regulation of physiologic hematopoiesis and in its alterations during infection.