bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL-8 specifically binds to endothelial but not to smooth muscle cells.
Authors: Schönbeck U , Brandt E , Petersen F , Flad H D , Loppnow H 
Published: December 2022

Abstract
The proinflammatory cytokine and potent chemoattractant IL-8 is involved in regulation of infectious or inflammatory processes. Human vascular endothelial cells (EC) and smooth muscle cells (SMC) probably contribute to these responses by recognition and/or production of rIL-8. We demonstrate here in competitive binding studies with radiolabeled rIL-8 that EC and fibroblasts, but not SMC, specifically bind IL-8 with low affinity. The binding was not saturated by ligand concentrations up to 80 nM 125I-rIL-8. Unlabeled neutrophil-activating peptide-2 competed the binding of 125I-rIL-8, although less potently than unlabeled rIL-8, as reported previously for polymorphonuclear neutrophils. In contrast, connective tissue-activating peptide III, platelet factor 4, or lysozyme did not reduce binding of 125I-rIL-8 to EC or fibroblasts. In accordance with these binding studies, EC and fibroblasts, but not SMC, expressed human IL-8 receptor type I mRNA. Neither cell type expressed mRNA for IL-8 receptor type II. Stimulation with IL-1 alpha or LPS did not alter the results obtained in PCR or binding studies. Although SMC did not express specific binding sites for IL-8, Western blot experiments showed that IL-1 alpha-, TNF-, or LPS-stimulated SMC released two major immunoreactive isoforms of IL-8 in a time- and dose-dependent manner. The m.w. were similar to IL-8 isoforms released by EC or mononuclear cells. The differential capacity of EC and SMC to produce IL-8 and express IL-8 binding sites indicates that vascular cell-derived IL-8 may contribute to differential regulation of infectious and inflammatory responses in the vessel wall.
Endogenous IL-6 and IL-10 contribute to the differentiation of CD40-activated human B lymphocytes.
Authors: Burdin N , Van Kooten C , Galibert L , Abrams J S , Wijdenes J , Banchereau J , Rousset F 
Published: December 2022

Abstract
This study was initiated to explore the contribution of endogenous cytokines to CD40-induced B cell proliferation and differentiation. First, both CD40 and Ag receptor (AgR) cross-linking induced purified tonsillar human B lymphocytes to secrete the same pattern of cytokines, including IL-1 beta, IL-6, IL-10, granulocyte-macrophage-CSF, and TNF-alpha, whereas IL-1 alpha, IL-2, IL-3, IL-4, IL-5, IL-7, granulocyte (G)-CSF, or IFN-gamma were not detected. Second, cotriggering of CD40 and AgR resulted in additive secretion of both IL-6 and IL-10. Addition of IL-4 to CD40-activated B cells increased IL-6 levels but decreased IL-10 levels. In contrast, exogenous IL-10 diminished IL-6 levels. Neutralization of IL-6 and IL-10 using blocking Abs did not alter CD40-induced B cell growth. In contrast, IL-6 neutralization markedly inhibited the IL-4-induced IgE secretion (57 +/- 10%) as well as the IgG and IgM production resulting from AgR and CD40 cotriggering (49 +/- 16.5 and 29.5 +/- 4.5%, respectively). Blocking IL-10 inhibited the IgA secretion (25 +/- 2.7%) obtained after CD40 activation and the production of IgG, IgA, and IgM (24.1 +/- 5.6, 25 +/- 8, and 42 +/- 6.5%, respectively) by B lymphocytes undergoing dual ligation of CD40 Ag and AgR. Simultaneous neutralization of both endogenous IL-6 and IL-10 resulted in an increased inhibition of Ig secretion for B cells cotriggered by CD40 Ag and AgR (65-75%). Thus, endogenously produced IL-6 and IL-10 are involved in the differentiation of CD40-activated B cell.
Intraembryonic origin of hepatic hematopoiesis in Xenopus laevis.
Authors: Chen X D , Turpen J B 
Published: December 2022

Abstract
The liver is a major site of hematopoietic stem cell differentiation during vertebrate development. Hepatic hematopoiesis is dependent on colonization of the organ by extrinsically derived stem cells which, in mammals, are thought to originate only in the yolk sac. However, in birds and amphibians two distinct embryonic stem cell sources have been identified. The yolk sac or extraembryonic compartment is associated with the developing vitelline veins, and the para-aortic or intraembryonic compartment is associated with the dorsal aortae and postcardinal veins. The homologous compartments in the Xenopus embryo are the ventral blood island (extraembryonic) and dorsal lateral plate (intraembryonic) mesoderms, which contribute to primitive larval erythrocyte and definitive late larval and adult erythroid populations, respectively. The role of these embryonic stem cell sources in hepatic hematopoiesis has not been determined. We have examined the development of hepatic hematopoiesis in Xenopus 2N/3N stem cell chimeras using two-color FACS analysis. DNA content was determined using Hoechst 33342, and subpopulations of hematopoietic cells were identified with specific mAbs. Here we show that hepatic erythrocytes, leukocytes, and B lymphocytes in the liver of Xenopus larvae were derived from stem cells that originated from the intraembryonic mesoderm.
IL-12 inhibits IL-4 synthesis in keyhole limpet hemocyanin-primed CD4+ T cells through an effect on antigen-presenting cells.
Authors: DeKruyff R H , Fang Y , Wolf S F , Umetsu D T 
Published: December 2022

Abstract
Although IL-12 is known to enhance IFN-gamma synthesis in unprimed CD4+ T cells, the effect of IL-12 on IL-4 synthesis in primed CD4+ T cells, which are thought to have relatively fixed cytokine profiles, has not been clearly examined. We examined the effects of IL-12 on cytokine production by CD4+ keyhole limpet hemocyanin (KLH)-primed memory lymph node T cells and by already established KLH-specific CD4+ T cell clones. First, we found that the presence of IL-12 greatly reduced the development of IL-4 synthesis in resting but not activated memory CD4+ T cells. Although IL-12 did not inhibit the production of IL-4 in cloned Th2 effector cells, it greatly inhibited the development of IL-4 synthesis in primed CD4+ T cells taken from the lymph nodes of mice previously immunized with KLH. Secondly, we found that IL-12 inhibited IL-4 synthesis either when directly added to cultures of T cells or when APC were preincubated in IL-12. Inasmuch as the enhancing effect of IL-12 on IFN-gamma synthesis occurred optimally only when the T cells were cultured directly in IL-12, these studies indicate that IL-12 affects IL-4 synthesis via a mechanism that involves APC, a process that differs from that by which it affects IFN-gamma synthesis. These studies also indicate that the administration of IL-12 would be clinically useful in treating patients, for example those with allergic disease or lepromatous leprosy, in whom memory T cells inappropriately overproduce IL-4.
NK cell recognition of MHC class I. NK cells are sensitive to peptide-binding groove and surface alpha-helical mutations that affect T cells.
Authors: Kurago Z B , Smith K D , Lutz C T 
Published: December 2022

Abstract
NK cells directly or indirectly recognize MHC class I molecules, but the exact structures recognized remain poorly defined. We address the hypothesis that NK cells, like T cells, directly contact peptide/MHC class I complexes. This hypothesis predicts that NK-mediated killing is inhibited by amino acid substitutions in the MHC class I peptide-binding groove and in solvent-accessible alpha-helical residues proposed to contact the TCR. In our model system, target cell HLA-B*0702 inhibited killing by unstimulated peripheral blood NK cells. NK-mediated killing was increased significantly by 6 of 11 peptide-binding groove mutations and 6 of 12 TCR contact site mutations, but only 1 of 6 mutations outside these sites. Many of the mutations that inhibited NK-mediated killing prohibited killing by 12 alloreactive CTL clones. These data suggest that NK receptors directly contact HLA-B*0702, focusing on the peptide-binding groove and surrounding alpha-helices. NK cell lines exhibited multiple HLA recognition patterns, which is consistent with nonuniform expression of MHC receptors by NK cells. We propose that NK cells, like alpha beta T cells and some anti-MHC Abs, directly or indirectly recognize MHC-bound peptides.
Analysis of the intra-epithelial lymphocyte compartment in SCID mice that received co-isogenic CD4+ T cells. Evidence that mature post-thymic CD4+ T cells can be induced to express CD8 alpha in vivo.
Authors: Morrissey P J , Charrier K , Horovitz D A , Fletcher F A , Watson J D 
Published: December 2022

Abstract
Severe combined immunodeficient (SCID) mice injected with co-isogenic CD4+/CD45RBhigh lymph node T cells from normal donors develop a wasting disease that is caused by hyperplasia of the intestinal epithelium. SCID mice injected with purified lymph node CD4+ T cells or CD4+/CD45RBlow T cells do not develop the disease. The IEL compartment from SCID mice injected with highly purified CD4+/CD45RBhigh T cells or CD4+ T cells contained significant numbers of T cells that expressed both CD4 and CD8 alpha, but not CD8 beta. The CDr+/CD8 alpha + T cells were unique to the IEL compartment of the small intestine and were not observed in significant numbers in the lamina propria, mesenteric lymph node, nor IEL compartment of the large intestine. By using Ly-5 mismatched donors and recipients, we determined that the CD4+/CD8 alpha + T cells were derived from the donor T cells. The expression of CD8 alpha was stable in vitro, and CD8 alpha mRNA was detected in sorted CD4+/CD8 alpha + T cells by reverse transcriptase-PCR (RT-PCR). Recombinase-activating gene (RAG)-1 and -2 mRNA was not detected in the intra-epithelial lymphocyte CD4+/CD8 alpha + T cell population. Thus, it appears that under conditions unique to the epithelial layer of the small intestine, mature post-thymic CD4+ T cells can be induced to express CD8 alpha.
Successive generation of antigen-presenting, dendritic cell lines from murine epidermis.
Authors: Xu S , Ariizumi K , Caceres-Dittmar G , Edelbaum D , Hashimoto K , Bergstresser P R , Takashima A 
Published: December 2022

Abstract
Dendritic cells are specialized APCs that exhibit an extraordinary capacity to activate naive T cells. Langerhans cells (LC), as epithelial tissue-specific members of this family, play key roles in the induction of T cell-mediated immunity against environmental, infectious, and tumor-associated Ags in skin. A major limitation in studying the biology of dendritic cells or LC has been the absence of stable, long-term cell lines. To overcome this limitation, we have established a series of APC lines (XS series) from newborn BALB/c mouse epidermis. XS lines, which have grown for more than 12 mo in culture, exhibit high similarity to LC freshly procured from skin in terms of: a) tissue of derivation (epidermis), b) phenotype (lalow/CD45+/E-cadherin+/B7-1-), c) shape (elongated dendrites), and d) Ag-presenting profile (modest ability to activate naive, allogeneic T cells and remarkable ability to present a protein Ag to primed CD4+ T cells). The availability of XS lines as well as the methodologies used for their growth enhance our capability of studying the biology of LC at biochemical and molecular levels.
Prostaglandin E2 release triggered by phagocytosis of latex particles. A distinct association with prostaglandin synthase isozymes in bone marrow macrophages.
Authors: Shibata Y 
Published: December 2022

Abstract
Previous studies showed that murine bone marrow-derived macrophages (M phi) induced in vitro by IL-3 express cellular prostaglandin G/H synthase (PGHS)-1 but not PGHS-2. To induce PGHS-2 in this study, the M phi were primed further with IFN-gamma plus LPS. The expression of the PGHS isozymes was determined by cytometric analysis using Abs against PGHS-1 and PGHS-2. The expression of PGHS-2, but not PGHS-1, was dexamethasone-sensitive. To assess PGE2-releasing capacity, the primed M phi were triggered by challenge with calcium ionophore A23187, the protein kinase C (PKC) activator PMA, exogenous arachidonic acid, and 1.1-micron latex bead particles. Our results showed that the primed M phi expressed both isozymes and responded to all challenges used to release a substantial amount of PGE2 (&gt; 10 ng PGE2/10(6) cells/ml), whereas the control unprimed M phi responded to A23187 and arachidonic acid but not to PMA or latex beads to release PGE2. However, the primed M phi did not release PGE2 when triggered with nonphagocytosable particles (&gt; or = 40 microns) or when pretreated with cytochalasin D before they were challenged with 1.1-micron beads. Furthermore, staurosporine, a PKC inhibitor, did not inhibit the PGE2 release triggered by the beads. PMA-triggered PGE2 release by the primed M phi, in sharp contrast, was staurosporine-sensitive but cytochalasin D-resistant. Our data suggest that there are multiple or alternative pathways for triggering PGE2 synthesis and release distinctively associated with two PGH synthase isozymes. It is of special interest that the novel pathway triggered by interiorization of particles is associated with the expression of PGHS-2.
Patterns of cytokine secretion by autoreactive proteolipid protein-specific T cell clones during the course of multiple sclerosis.
Authors: Correale J , Gilmore W , McMillan M , Li S , McCarthy K , Le T , Weiner L P 
Published: December 2022

Abstract
To determine whether cytokine secretion patterns change with disease status in patients with multiple sclerosis (MS), we measured IFN-gamma, TNF-alpha beta, IL-4, IL-6, IL-10 and TGF-beta secretion in a panel of T cell clones (TCCs) specific for proteolipid protein (PLP) after stimulation with PLP peptides or polyclonal activators. During acute attack, the predominant pattern of cytokine secretion resembled that of murine Th1 cells; i.e, IFN-gamma and TNF-alpha beta, and appeared to be restricted to PLP-reactive TCCs. None of the TCCs isolated during acute attack produced TGF-beta in response to PLP, Con A, or anti-CD3 Ab. Half of these TCCs were, however, capable of TGF-beta secretion and mRNA expression upon stimulation with PMA and the calcium inonphore A23187, suggesting a possible defect in activation through the TCR/CD3 pathway. During remission in the same patients all but two PLP-TCCs showed patterns of cytokine secretion resembling that of murine Th0, Th1, and Th2 subsets. The levels of IL-10 secreted by these TCCs were significantly higher than those of TCCs isolated during acute attacks and those derived from normal subjects and patients with other noninflammatory neurologic diseases. Furthermore, 50% of these TCCs were capable of producing TGF-beta after Ag-specific or polyclonal stimulation. All TCCs isolated from control subjects exhibited a Th0 like secretion profile. These data indicate that different stages of disease in MS are characterized by different patterns of cytokine secretion by PLP-specific TCCs, suggesting a role for cytokines in clinical events during the course of MS.
Correction of proliferative responses in purine nucleoside phosphorylase (PNP)-deficient T lymphocytes by retroviral-mediated PNP gene transfer and expression.
Authors: Nelson D M , Butters K A , Markert M L , Reinsmoen N L , McIvor R S 
Published: December 2022

Abstract
Purine nucleoside phosphorylase (PNP; EC 2.4.2.1) deficiency is associated with a fatal T cell immunodeficiency in children, a candidate condition for gene therapy by introduction of functional PNP sequences into either T lymphocytes or more primitive progenitor cells in the bone marrow. To test the effectiveness of PNP gene transfer in T lymphocytes, a retroviral vector (LmPSN-2) was designed and constructed to express the murine PNP cDNA under transcriptional regulation of the Moloney murine leukemia virus long terminal repeat. LmPSN-2 was first used to mediate gene transfer and expression of electrophoretically distinct murine PNP in normal (PNP-positive) human PBL. Peripheral blood leukocytes were then obtained from a PNP deficient patient and characterized phenotypically. Despite their paucity and general mitogenic unresponsiveness, T lymphocytes from this patient were successfully grown in culture by using anti-CD3 with rIL-2 and then transduced with LmPSN-2. Elevated PNP enzyme activity was observed in the transduced cell population. Mitogenic and allogeneic responses, normally depressed in PNP-deficient patients' cells, were partially corrected in the transduced cell population relative to nontransduced cells. These results suggest the possibility of effecting improved immunologic function in PNP-deficient T lymphoid cells by retroviral-mediated gene transfer as therapy for PNP deficiency.
Inhibition of the induction of delayed-type and contact hypersensitivity by calcitonin gene-related peptide.
Authors: Asahina A , Hosoi J , Beissert S , Stratigos A , Granstein R D 
Published: December 2022

Abstract
Calcitonin gene-related peptide (CGRP)-containing nerves are frequently associated anatomically with epidermal Langerhans cells (LC), and LC Ag-presenting function is down-regulated by CGRP. To investigate possible regulation of cutaneous immunity by CGRP, we examined its effect on the induction of delayed-type hypersensitivity (DTH) and contact hypersensitivity (CHS). A system of immunity to the murine spindle cell tumor S1509a (H-2a) was employed to examine induction of DTH by LC. This system requires exposure of epidermal cells (EC) to GM-CSF for induction of substantial immunity. EC were prepared from CAF1 mice (H-2a/d) and Thy-1+ cells deleted. EC were exposed for 16 h to GM-CSF with or without CGRP. EC were then pulsed with tumor-associated Ags (TAA), washed, and injected s.c. into mice three times at 7-day intervals for immunization. Mice were challenged for a DTH response by injection of a hind footpad with TAA-pulsed EC, and 24-h footpad swelling assessed. Exposure of EC to CGRP significantly inhibited induction of DTH. To examine the effect of CGRP administered in vivo on induction of immunity, 530 pmol of CGRP or diluent alone was injected intradermally into the dorsum of the left ear of naive mice 8 h and 3 h before epicutaneous application of a hapten at the injected site. Mice were challenged on the right ear 7 days later and 24 h ear swelling was assessed. CGRP significantly inhibited the induction of CHS whereas calcitonin had no effect. Furthermore, when hapten was applied at a site distant from CGRP administration, no inhibition of CHS was observed, suggesting that the effect of CGRP is local. These data support the concept that CGRP may be an endogenous regulator of immune function and also suggest the possibility that CGRP or its analogues administered in vivo might have therapeutic utility as immunomodulators.
Induction of autoantibody responses to GM-CSF by hyperimmunization with an Id-GM-CSF fusion protein.
Authors: Chen T T , Levy R 
Published: December 2022

Abstract
Fusion proteins consisting of an Ig containing xenogenic constant regions and granulocyte-macrophage colony stimulating factor (Id-GM-CSF) are potent immunogens capable of inducing anti-idiotypic Abs after two immunizations, without the usual need for adjuvants or carrier proteins. In this study, we investigated the effects of hyperimmunization with Id-GM-CSF and found that it induces anti-GM-CSF Abs that could bind to GM-CSF and neutralize its bioactivity in vitro. However, no detrimental effects of the anti-GM-CSF activity were apparent on the general health of the animals or on their base line white blood cell counts. Mice with the anti-GM-CSF activity reconstituted their peripheral white blood cells with identical kinetics as control mice after high dose cyclophosphamide treatment, sublethal irradiation, or lethal irradiation followed by syngeneic bone marrow transplantation. Primary and secondary Ab responses to a variety of protein Ags, including an unrelated Ig Id, were not affected. However, the anti-Id response induced by an unrelated GM-CSF fusion protein that is dependent upon the GM-CSF bioactivity was impaired. To avoid any potential problems associated with inducing anti-GM-CSF Abs, we show that priming with the Id-GM-CSF protein and boosting with the Id protein alone were sufficient to induce comparable anti-Id titers without inducing anti-GM-CSF Abs. We conclude that although hyperimmunization of mice with the GM-CSF fusion protein induced neutralizing anti-GM-CSF Abs, this was of little consequence to the animals. Nevertheless, we have devised a strategy to overcome this potential limitation on the use of GM-CSF fusion proteins for immunization.
In vitro effects of HgCl2 on murine lymphocytes. I. Preferable activation of CD4+ T cells in a responder strain.
Authors: Jiang Y , Möller G 
Published: December 2022

Abstract
Mercury-induced autoimmune disorders have been demonstrated in rats and mice injected with HgCl2. We have studied the ability of HgCl2 to activate murine lymphocytes in vitro and found that it induced increased DNA synthesis, which peaked at days 4 to 6. Other metal ions, such as Mg2+ and Zn2+, had no or much less effect. Consistent with the in vivo studies, there were strain differences, and the most significant increase in thymidine uptake was induced in A.SW and BALB/c spleen cells. Both T lymphocytes and adherent cells were required for activation, and anti-CD4 Ab completely abrogated HgCl2-induced proliferation, suggesting the involvement of T helper cells. Cell phenotype analysis demonstrated that HgCl2 induced both proliferation and transformation of CD4+ and CD8+ T cells from BALB/c mice (responder strain). In contrast, only CD8+ T cells from the nonresponder DBA/2 mice were transformed. These findings indicate that helper T cells play a crucial role for the immunologic effects caused by HgCl2 and determine the ability of different mouse strains to respond to HgCl2.
CD28 cross-linking augments TCR-mediated signals and costimulates superantigen responses.
Authors: Ohnishi H , Ledbetter J A , Kanner S B , Linsley P S , Tanaka T , Geller A M , Kotb M 
Published: December 2022

Abstract
The CD28 molecule expressed on the surface of T cells plays a pivotal role in transducing costimulatory signals necessary for cell activation. CD28 coligation enhances tyrosine phosphorylation and phosphoinositol 3-kinase association in responsive cells. CD28 cross-linking has also been reported to activate inositol phospholipid turnover and to cause release of intracellular calcium. Here we examine the effects of CD28 cross-linking on early activation of protein kinase C (PKC). We have reported recently that either PMA or CD28 cross-linking synergizes with signals delivered by superantigen and cytokines to induce the proliferation of APC-depleted T cells. Unlike PMA, CD28 cross-linking alone failed to induce an increase in membrane-associated PKC activity. However, PKC activation was seen in resting T cells when CD28 was cross-linked in the presence of superantigen plus APC-derived supernatant, which by themselves had no effect on PKC activity. Inhibition of PKC activity using calphostin C blocked the response of pure T cells to superantigen in the presence of either autologous APC, PMA, or CD28 cross-linking. This effect was specific; it was only seen when calphostin C was added within the first hour of stimulation. Assays of [Ca2+]i levels showed that CD28 cross-linking augmented and prolonged the rise in [Ca2+]i induced in T cells by superantigen and APC-derived cytokines. In the presence of superantigen, the proliferative response of T cells costimulated by CD28 cross-linking was cyclosporin A-sensitive, whereas in the presence of PMA, CD28 cross-linking conferred resistance to cyclosporin A. Both the phosphorylation of phospholipase C gamma 1 at tyrosine and the rise in [Ca2+]i induced by CD28 cross-linking in preactivated T cells were blocked by herbimycin A. Herbimycin A treatment also blocked the ability of CD28 cross-linking to induce a rise in [Ca2+]i in resting T cells. We conclude that CD28 costimulatory signals augment superantigen-induced TCR signals by converging onto common TCR effector pathways involving the activation of phospholipase C gamma 1 and PKC and by generating a cyclosporin A-sensitive pathway.