bluuebunny/crossref_metadata_2025_split huggingface dataset:
Usage of a novel class of germ-line Ig variable region gene for cationic anti-DNA autoantibodies in human lupus nephritis and its role for the development of the disease.
Authors: Harada T , Suzuki N , Mizushima Y , Sakane T 
Published: December 2022

Abstract
It has been shown that cationic anti-DNA autoantibodies have nephritogenic potential in murine models of lupus nephritis. We have recently reported the close relationship between the presence of cationic anti-DNA Abs and the development of lupus nephritis in humans. To investigate underlining mechanisms responsible for the production of pathogenic autoantibodies, we have isolated a cDNA clone (SC17) encoding cationic anti-DNA Ab of human systemic lupus erythematosus with severe nephritis that was present at the onset of disease but disappeared after disease remission with corticosteroids. We have also cloned a counterpart Ig VL germ-line gene (SG3) from purified neutrophils of the patient and found the presence of replacement mutations only in the CDR of SC17. Surprisingly, predicted isoelectric point (pI) of deduced protein encoded by SG3 was the most cationic one among those encoded by previously reported human V kappa germ-line genes in the DNA database. These results raise the possibility that the use of specific germ-line genes may confer a cationic charge on the anti-DNA Ab, whereas somatic mutations induce affinity maturation of anti-DNA Ab in human lupus nephritis. Anti-DNA Ab-secreting B cells, but not DNA nonbinding B cells of the same patient, constitutively expressed SC17 mRNA. This mRNA is also expressed by B cells from a vast majority of patients at the onset of disease or exacerbation of lupus nephritis. However, the mRNA is absent in B cells from patients with lupus nephritis during disease remission, systemic lupus erythematosus patients without renal involvements, and normal individuals. It is suggested that the SC17 mRNA expression of B cells is rather restricted to systemic lupus erythematosus patients with active renal involvements.
Expression of adhesion molecules, platelet-activating factor, and chemokines by Kaposi's sarcoma cells.
Authors: Sciacca F L , Stürzl M , Bussolino F , Sironi M , Brandstetter H , Zietz C , Zhou D , Matteucci C , Peri G , Sozzani S 
Published: December 2022

Abstract
The present study was designed to investigate whether cells cultured from Kaposi's sarcoma (KS), a vascular tumor with a prominent leukocyte infiltration, express molecules important for the recruitment and activation of leukocytes. KS cells expressed intercellular adhesion molecule-1, which was augmented by exposure to IL-1 beta or TNF-alpha. Unlike endothelial cells, resting or cytokine-activated KS cells did not express appreciable levels of intercellular adhesion molecule-2, vascular cell adhesion molecule-1, and E-selectin on their surface. Weak expression of vascular cell adhesion molecule-1 mRNA was detectable by Northern blot analysis and, most clearly, by PCR analysis. Upon exposure to inflammatory cytokines, KS cells produced the attractant/activating lipid platelet-activating factor. KS cells expressed appreciable levels of the chemotactic cytokines, monocyte chemotactic protein-1 (MCP-1) and IL-8, as determined by Northern blot analysis, immunoassay, or bioassay. Chemokine production was augmented by IL-1 beta or TNF-alpha. MCP-1 expression was also detected in KS lesions by in situ hybridization. The set of molecules identified in the present study is probably important in determining the prominent leukocyte infiltration observed in KS. Tumor-associated leukocytes may amplify autocrine/paracrine circuits that sustain KS proliferation and contribute to recruitment of host vascular cells.
Cloned human CD8+ cytotoxic T lymphocytes protect human peripheral blood leukocyte-severe combined immunodeficient mice from HIV-1 infection by an HLA-unrestricted mechanism.
Authors: van Kuyk R , Torbett B E , Gulizia R J , Leath S , Mosier D E , Koenig S 
Published: December 2022

Abstract
The ability to infect human peripheral blood leukocyte-reconstituted severe combined immunodeficient (hu-PBL-SCID) mice with HIV has allowed evaluation of several strategies for preventing or treating infection. In one study, hu-PBL-SCID mice derived from HIV gp160-vaccinated donors were shown to resist HIV infection, and resistance correlated best with in vitro assays of cellular immunity. We have assessed directly the importance of cellular immunity to HIV in the present experiments by the adoptive transfer of HLA-A3-restricted HIV-1 Nef-specific or HLA-B14-restricted Gag-specific CD8+ CTL clones to SCID mice bearing HLA-matched or mismatched PBL grafts. Multiple inoculations of CTL before and after HIV-1 exposure protected HLA-matched hu-PBL-SCID mice from infection, but initiation of CTL therapy on the same day as HIV infection was much less effective. However, at the high numbers of CTL required for complete protection from HIV infection, many HLA-mismatched hu-PBL-SCID mice were also protected by pre-exposure CTL transfer. Transfer of CTL with a different specificity (HTLV-1 Tax) to HLA-matched hu-PBL-SCID mice also afforded partial protection. These results suggest that HLA-restricted cytotoxicity may be less important than other nonspecific effector mechanisms for the inhibition of HIV-1 infection in vivo.
IL-12 is expressed and released by human keratinocytes and epidermoid carcinoma cell lines.
Authors: Aragane Y , Riemann H , Bhardwaj R S , Schwarz A , Sawada Y , Yamada H , Luger T A , Kubin M , Trinchieri G , Schwarz T 
Published: December 2022

Abstract
IL-12 is a 70-kDa heterodimeric cytokine composed of two covalently linked chains, p40 and p35. IL-12 has multiple effects on T and NK cells and recently was found to be required for optimal Th1 cell development. In a variety of inflammatory skin disorders including delayed type hypersensitivity and contact hypersensitivity, Th1 cells appear to be critically involved. Because keratinocytes are well known to exhibit the capacity to release a variety of proinflammatory and immunologic cytokines, and thereby to be able to modulate inflammatory and immune reactions within the skin, it was investigated whether human keratinocytes and keratinocyte cell lines can release IL-12. Supernatants of phorbol-12,13-dibutyrate (PDBu) stimulated human epidermoid carcinoma cell lines (KB, A431) induced IFN-gamma production by PBL. This activity could be completely blocked by the addition of an anti-IL-12 Ab directed against the p40 subunit of IL-12 (C8.6). Release of IL-12 by keratinocyte cell lines was further confirmed by an RIA specific for p40. Immunoprecipitation under reducing conditions using the C8.6 Ab yielded specific bands at 40 kDa in supernatants of both KB cells and normal human keratinocytes. Northern blot analysis revealed IL-12-specific mRNA transcripts in PDBu-treated KB cells using cDNA probes encoding for p35 and p40. Moreover, by reverse transcription PCR specific transcripts for p35 and p40 were found in keratinocytes. These data indicate that keratinocyte cell lines and, although to a much lesser degree, normal human keratinocytes, exhibit the capacity to make IL-12; thus demonstrating for the first time IL-12 production by nonhemopoietic cells. Thus, one may speculate that keratinocytes via this capacity may influence the fate of Th-mediated immune responses, favoring Th1 responses by enhanced production of IL-12 or Th2 responses by reduced IL-12 release.
CD44 is a cytotoxic triggering molecule in human peripheral blood NK cells.
Authors: Sconocchia G , Titus J A , Segal D M 
Published: December 2022

Abstract
Previous studies have shown that target cells that bind to CD44 adhesion molecules on cloned cytotoxic T cells are lysed by the CTL. To determine whether CD44 is also a cytotoxic trigger molecule in human PBL, we tested a bispecific Ab consisting of anti-CD44 Fab cross-linked to a Fab against a target cell Ag, in cytotoxicity assays using PBL as effectors. We found that PBL mediated lysis in the presence of the anti-CD44 bispecific Ab provided that the effector cells were stimulated with either IL-2 or IL-12. Cell fractionation experiments showed that CD44-directed cytolysis was mediated exclusively by CD56+ low buoyant density cells, mainly by NK (CD16+) cells, but also to a lesser extent by CD56+ T cells. CD44-directed cytolysis appeared in these subsets 24 to 48 h after addition of IL-2 and paralleled the acquisition of Ab-independent (LAK) activity; in contrast, these cells mediated Ab-dependent cellular cytotoxicity and CD3 redirected lysis before stimulation with IL-2. Unstimulated CD56+ cells uniformly expressed high levels of CD44 that increased modestly after incubation with IL-2. No changes in isoform expression in the extracellular domain of CD44 could be detected upon activation with the use of isoform-specific mAbs. Thus, lymphokine stimulation caused CD44 to become a cytotoxic trigger in subsets of PBL that mediated other forms of cytotoxicity and expressed CD44 before activation, suggesting that activation of these cells was accompanied by a coupling of CD44 to their lytic machinery.
TCR selection and allelic exclusion in RAG transgenic mice that exhibit abnormal T cell localization in lymph nodes and lymphatics.
Authors: Wayne J , Suh H , Sokol K A , Petrie H T , Witmer-Pack M , Edelhoff S , Disteche C M , Nussenzweig M C 
Published: December 2022

Abstract
RAG-1 and RAG-2 are developmentally regulated genes that are essential for V(D)J recombination and lymphocyte development. Expression of RAG-1 and RAG-2 by thymocytes is normally limited to cells that have not completed selection. We have previously documented that persistent expression of the recombinase activating genes (RAG) in transgenic mice results in aberrant thymic development, altered lymphatic microanatomy, and a profound immunodeficiency. Here we further document the pathologic changes found in TG.RAG-1,2 mice and examine the role of TCR recombination and positive and negative thymic selection, as well as allelic exclusion, in the etiology of the phenotype. We find that neither selection nor TCR allelic exclusion can be overcome by transgenic expression RAG-1 and RAG-2 under the control of an lck promoter.
CD43 (S7) expression identifies peripheral B cell subsets.
Authors: Wells S M , Kantor A B , Stall A M 
Published: December 2022

Abstract
CD43 (leukosialin) expression has previously been demonstrated on the surface of developing B cells in mouse bone marrow and on plasma cells induced in vitro, but not on peripheral B cells in spleen. Here we show that CD43, as recognized by mAb S7, is indeed expressed on a small population of splenic B cells. Flow cytometric phenotyping of normal mice and radiation chimeras reveals that CD43/S7 is expressed on virtually all (&gt; 90 to 95%) splenic B-1 cells and the majority of peritoneal B-1 cells, but not on conventional B cells. The expression of CD43/S7, in conjunction with other cell surface markers, clearly distinguishes B-1 cells from follicular, marginal zone, and immature B cells in the unstimulated adult spleen and permits further phenotyping of these subsets. The phenotype of splenic and peritoneal B-1 cells in normal BALB/c and BAB/25 mice is essentially identical with the exception that all peritoneal B-1 cells express CD11b (Mac-1) and some lack CD43/S7 and heat stable Ag (as detected by the mAb 53-10) expression. Although splenic B-1, marginal zone, and immature B cells share many phenotypic characteristics, these studies show that, in addition to CD43, they differ with respect to the expression levels of a variety of Ags including heat stable Ag, B220, and the B cell activation Ag B7.
Novel allele-specific, post-translational reduction in HLA class I surface expression in a mutant human B cell line.
Authors: Greenwood R , Shimizu Y , Sekhon G S , DeMars R 
Published: December 2022

Abstract
Human B cell line .220 has a novel defect in HLA class I cell surface expression. Mutant .220 was derived from .184TGr, from which both copies of HLA-A and -B are deleted, and has less surface HLA-C than .184TGr. Transfer of class I genes into .220 revealed allele-specific reductions in surface expression: HLA-A1 and -B8 were 1 to 21% of normal; HLA-A11, -A24, and -B5 were moderately reduced; and HLA-A2, -A3, and -B7 were reduced little, if at all. Class I mRNA in .220(A1) and .220(B8) transferents is normal in size and at least normal in quantity. Surface expression of class I molecules was restored by fusing .220 transferents with mutant .174, which lacks the TAP-1 and -2 genes needed for transport of class I-binding peptides. Fusion of .220(A1) cells with beta 2-microglobulin-deficient Daudi cells also fully restored surface expression of class I molecules encoded by both parental cells, indicating beta 2-microglobulin is functional in .220. Pulse-chase experiments showed transgene-encoded HLA-A1 and -B8 alpha-chains are made in apparently normal amounts and associate with beta 2-microglobulin in .220. However, post-translational processing of the HLA-A1 and -B8 molecules is retarded in or before the Golgi apparatus, and immunoprecipitable HLA-A1 molecules disappear after their synthesis. The effects of these abnormalities on surface expression of class I molecules were reversed by incubating .220(A1) and .220(B8) cells at 21 degrees C, which greatly increased the amounts of cell surface HLA-A1 and -B8.
Expressed swine VH genes belong to a small VH gene family homologous to human VHIII.
Authors: Sun J , Kacskovics I , Brown W R , Butler J E 
Published: December 2022

Abstract
The sequences of 34 swine H chain V-regions expressed with either IgG, IgA, or IgM C regions in adult swine and newborn piglets are described and compared. Sixteen of these V-regions were cloned by using a specific leader primer whereas 18 were cloned by anchored PCR. According to the operational criterion of VH family classification, i.e., &gt; 80% DNA sequence similarity, all sequences belong to a homogeneous VH gene family. A total of 31 additional VH-bearing C mu clones obtained by anchored PCR from colostrum-deprived newborn piglets hybridized equally with a probe for C mu and a pan-VH probe. When the consensus sequence of the expressed swine VH genes were compared with those of VH gene for humans (VHI, II, III), mouse (VHI, II, III), rabbit, and chicken, swine VH genes seem to have common ancestry with the human VHIII family, rabbit VH genes, and the single functional VH gene of the chicken. The leader peptides of all clones obtained by anchored PCR showed &lt; 1% variability, and the deduced amino acid sequences from aa4 to aa25 in all 34 clones are identical. Framework (FR)1 and FR2 are conserved whereas FR3 shows greater variability. A total of 23 of 30 JH sequences were identical, suggesting preferential use of one JH. This frequent, putative JH sequence is not similar to any JH gene in humans. Identical genomic Southern hybridization patterns, each with 13 bands of differing intensity and regardless of stringency, were obtained when either a leader or a pan-specific VH probe was used. Analyses of individual genomic bands by single strand conformational polymorphism and sequence analysis suggest that the number of VHIII-related genes in the swine genome is &lt; 20.
Construction, expression, and immunogenicity of multiple tandem copies of the Schistosoma mansoni peptide 115-131 of the P28 glutathione S-transferase expressed as C-terminal fusions to tetanus toxin fragment C in a live aro-attenuated vaccine strain of Salmonella.
Authors: Khan C M , Villarreal-Ramos B , Pierce R J , Demarco de Hormaeche R , McNeill H , Ali T , Chatfield S , Capron A , Dougan G , Hormaeche C E 
Published: December 2022

Abstract
Genetic fusions have been constructed between the highly immunogenic but atoxic fragment C of tetanus toxin and a guest peptide, aa115-131, from the protective 28-kDa glutathione S-transferase Ag of Schistosoma mansoni. Fusions have been assembled to express one, two, four, and eight tandem copies of the peptide. The recombinant vectors have been electroporated into the nonvirulent aroA strain of Salmonella typhimurium SL3261. The fusion proteins are soluble and stably expressed in Salmonella as evaluated by Western blotting with fragment C and glutathione S-transferase antisera. Mice have been immunized i.v. with a single dose of the live recombinant salmonellae. The strains are stable in mice and elicit Ab responses directed against fragment C, as determined by enzyme-linked immunosorbent assays. Ab responses were also detected against the guest peptide. The Ab responses improved dramatically toward the aa115-131 peptide with increasing copy number, with the octameric "repitope" fusion displaying the greatest potency. This approach may represent a general strategy for eliciting immune responses against peptides in live bacterial vaccines.
IL-2-dependent NK cell responses discovered in virus-infected beta 2-microglobulin-deficient mice.
Authors: Su H C , Orange J S , Fast L D , Chan A T , Simpson S J , Terhorst C , Biron C A 
Published: December 2022

Abstract
In vivo NK cell responses to lymphocytic choriomeningitis virus were studied in CD8+ T cell-deficient mice. On day 7 after infection, dramatically elevated splenic NK cell activities were observed in both beta 2-microglobulin-negative (beta 2-m-/-) mice deficient in CD8+ T cells and anti-CD8-treated C57BL/6 animals. The enhanced responses could be attributed to increased numbers of activated NK1.1+CD3- cells. The day 7 NK cell responses in beta 2-m-/- mice, but not in normal C57BL/6 animals, were cyclosporin A sensitive and coincided with IL-2 production and high affinity IL-2R expression on NK cells. Proof that IL-2 played an essential role in day 7 responses was provided by the observation that IL-2-/- x beta 2-m-/- mice lacked the late NK cell activation. Taken together, these results showed that NK cells can be activated and expanded by an IL-2-dependent pathway. Because these responses can only be measured in the absence of CD8+ T lymphocytes, an exciting model of networking between T and NK cells in response to viruses is postulated.
LPS induces selective translocation of protein kinase C-beta in LPS-responsive mouse macrophages, but not in LPS-nonresponsive mouse macrophages.
Authors: Shinji H , Akagawa K S , Yoshida T 
Published: December 2022

Abstract
Translocation of protein kinase C (PKC) after PMA or LPS stimulation has been studied in thioglycolate (TGC)-elicited murine peritoneal macrophages. Among the PKC subtypes we examined (alpha, beta, gamma, delta, and epsilon) by indirect immunostaining and immunoblot analysis, conventional PKC-beta, as well as novel PKC-delta and PKC-epsilon were found to exist in TGC-elicited C3H/HeN mouse macrophages. Translocation of PKC-beta to the Triton-stable cytoskeleton could be seen in macrophages after stimulation by both PMA and LPS. On the other hand, novel PKCs redistributed only after PMA stimulation. Macrophages obtained from LPS-nonresponsive C3H/HeJ mice also exhibited PKC-beta, and the m.w., cellular distribution, and cellular content of this enzyme could not be distinguished from those of C3H/HeN macrophages. These macrophages exhibited PKC-delta and PKC-epsilon, as did the C3H/HeN macrophages. In these macrophages, however, LPS did not induce any remarkable change in the intracellular distribution of PKC-delta and PKC-epsilon or PKC-beta, whereas PMA was able to induce the translocation of PKC-beta to the cytoskeleton. These results suggest that LPS stimulation induces selective redistribution of PKC-beta in LPS-responsive macrophages, whereas a defect related to LPS unresponsiveness exists in C3H/HeJ mouse macrophages before the PKC activation. Translocation of PKC-beta can be understood to be an important event in LPS signaling in macrophages.
IL-10 is induced during HIV-1 infection and is capable of decreasing viral replication in human macrophages.
Authors: Akridge R E , Oyafuso L K , Reed S G 
Published: December 2022

Abstract
IL-10 has been shown to be capable of down-regulating several aspects of macrophage function. This study was undertaken to define the association between IL-10 and HIV-1 infection in human macrophages. Infection of macrophages with a monocytotropic strain of the human immunodeficiency virus, HIV-BaL, resulted in expression of IL-10 mRNA within 3 to 12 h after infection, as determined by the reverse transcriptase PCR. Biologically active IL-10 was detected in supernatants from HIV-1-infected macrophages as early as 12 h post-infection. The addition of human rIL-10 to HIV-1-infected macrophage cultures resulted in a significant decrease in the viral replication. In addition, exogenous IL-10 blocked the ability of TNF-alpha to elevate viral replication. To determine whether IL-10 was associated with in vivo infection, lymph nodes from AIDS patients were examined for the presence of IL-10 mRNA by using PCR. IL-10 mRNA was evident in all lymph node tissue examined, but was absent in normal lymph node biopsies. These in vitro and in vivo findings demonstrate a strong and heterogeneous association between HIV-1 infection and IL-10.
The role of CD40-CD40 ligand interaction in human T cell-B cell collaboration.
Authors: Nishioka Y , Lipsky P E 
Published: December 2022

Abstract
Interactions between CD40 on B cells and its ligand on activated T cells have been reported to play an important role in T cell-B cell collaboration. In this current study, a mAb against the human CD40 ligand (5c8) was used to investigate the impact of CD40-CD40 ligand interactions in the initial activation of normal human peripheral blood B cells and in subsequent proliferation and differentiation. B cells were activated by co-culture with anti-CD3-stimulated normal T cells. mAb against CD40 ligand blocked initial T cell-dependent B cell activation, as assessed by [3H]uridine incorporation and IL-2R expression. Subsequent B cell proliferation and differentiation were also inhibited by this mAb. In addition to its effect on B cell activation, 5c8 also inhibited the capacity of B cells to augment IL-2 production by anti-CD3 activated T cells, implying a role for CD40-CD40 ligand interactions in the accessory function of B cells. Despite the importance of CD40-CD40 ligand interactions in T cell-B cell collaboration, CD40 ligand-deficient T cell clones were found to induce initial activation of B cells and support Ig production. This effect was only marginally effected by mAb to LFA-1 and ICAM-1, suggesting that additional interaction molecules play a role in T cell-B cell collaboration. Taken together, the data indicate that CD40-CD40 ligand interactions plays an important role in T cell-dependent B cell activation and subsequent differentiation but additional interaction structures are also involved in T cell-B cell collaboration.