bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential chemotactic activities of sensory neuropeptides for human peripheral blood mononuclear cells.
Authors: Schratzberger P , Reinisch N , Prodinger W M , Kähler C M , Sitte B A , Bellmann R , Fischer-Colbrie R , Winkler H , Wiedermann C J 
Published: December 2022

Abstract
We studied the chemotactic effects of calcitonin gene-related peptide, vasoactive intestinal peptide, substance P (SP), and secretoneurin on PBMC and PBL using micropore filter assays. All four peptides induced migration of PBMC, whereas only calcitonin gene-related peptide, vasoactive intestinal peptide, and SP were chemotactic for PBL. Secretoneurin, known to induce monocyte chemotaxis, was unable to affect lymphocyte migration. Effects of SP on PBL were characterized by checkerboard analyses and represented true chemotaxis. Both T and B cells responded chemotactically to SP, the functional activity of SP residing in its C-terminal amino acid sequence. Involvement of neurokinin (NK) receptors was supported by inhibition of SP-induced migration of PBL with an NK1 receptor antagonist and induction of migration with [Sar9, Met(O2)11]SP and [PyrGlu6, Pro9]SP(6-11), two specific agonists for NK1 receptors, but not with [beta-Ala8]NK A(4-10), an agonist for NK2 receptors. PBL chemotaxis to SP was abolished by inhibition of tyrosin kinase but not by that of protein kinase C. Preincubation of PBL with pertussis or cholera toxin inhibited SP chemotaxis, indicating that in PBL, NK receptors for chemotaxis probably are coupled with G protein and involve a tyrosin kinase signaling pathway. We conclude that, together with calcitonin gene-related peptide and vasoactive intestinal peptide, SP is a lymphocyte chemoattractant, whereas secretoneurin, which is coreleased from sensory nerve endings, is not.
Chemokines are expressed in a myeloid cell-dependent fashion and mediate distinct functions in immune complex glomerulonephritis in rat.
Authors: Wu X , Dolecki G J , Sherry B , Zagorski J , Lefkowith J B 
Published: December 2022

Abstract
Using anti-glomerular basement membrane nephritis in rats, we investigated the mechanisms underlying in situ chemokine expression and the in vivo function of these cytokines during the acute phase of this model. We observed that CXC chemokine expression was monophasic and paralleled neutrophil (PMN) influx, whereas CC chemokine expression was biphasic with peaks coinciding with the influx of PMNs and macrophages (Mphi). The initial peak of chemokine expression was attenuated by decomplementation, neutropenia, and leukopenia, while the latter peak was attenuated only by leukopenia and augmented in the accelerated form of this disease model, corresponding to an increase in Mphi influx. Differential expression of chemokines by PMNs and Mphi was not an intrinsic property of these cells, as these leukocytes expressed similar profiles of chemokines in vitro. Immunostaining for Mphi inflammatory protein-1alpha, a CC chemokine, in acute nephritis validated that expression during acute nephritis was accompanied by local protein production. Moreover, neutralizing Ab to Mphi inflammatory protein-1alpha attenuated the acute phase proteinuria, but not the accompanying influx of PMNs. Neutralizing Ab to cytokine-induced neutrophil chemoattractant (a CXC chemokine), in comparison, inhibited both PMN influx and proteinuria. A combination of both Abs was not significantly more effective than either alone. In sum, the influx of myeloid cells is necessary for local chemokine expression in anti-glomerular basement membrane nephritis, although the differential expression of CXC and CC chemokines must involve additional factors. CXC and CC chemokines also mediate distinct, but overlapping, pathophysiologic roles in the acute phase of this model.
Lipopolysaccharide-binding protein and soluble CD14 transfer lipopolysaccharide to phospholipid bilayers: preferential interaction with particular classes of lipid.
Authors: Wurfel M M , Wright S D 
Published: December 2022

Abstract
LPS-binding protein (LBP) catalyzes the movement of LPS (endotoxin) from micelles directly to high density lipoprotein (HDL) particles, and this activity results in neutralization of the biologic activities of LPS. LBP also catalyzes the transfer of LPS to HDL by a two-step mechanism in which LPS is transferred to soluble CD14 (sCD14), and then from LPS-sCD14 complexes to HDL. In this work, we show that the phospholipid component of HDL, phosphatidylcholine (PC), is both necessary and sufficient for LBP-catalyzed neutralization of LPS through either mechanism. Our observation that LBP and sCD14 can transport LPS into phospholipid bilayers suggests that LBP and membrane CD14 may transport LPS into the phospholipid bilayer of cells such as monocytes and neutrophils. Studies with a variety of purified phospholipids showed that: 1) PC, phosphatidylserine, phosphatidylinositol, and sphingomyelin can neutralize LPS, while phosphatidylethanolamine, ceramide, and lactosylceramide cannot. 2) PC containing saturated long chain acyl groups (distearoyl-PC) does not neutralize LPS, but PC containing unsaturated long chain acyl groups (dioleoyl-PC) rapidly neutralizes LPS. 3) Inclusion of sCD14 is absolutely necessary to observe LBP-dependent neutralization of LPS by sphingomyelin, globoside, and phosphatidylserine. 4) Inclusion of sCD14 enhances movement to longer chain PC vesicles, but slows movement to certain short chain vesicles. These findings indicate that LBP and sCD14 will rapidly transfer LPS to certain membranes based on the kinetics of the movement of LPS into these membranes. This discrimination may target LPS to certain classes of lipoprotein, certain cell types, or even certain lipid domains at the cell surface.
Endotoxin and IL-1 hyporesponsiveness in a patient with recurrent bacterial infections.
Authors: Kuhns D B , Long Priel D A , Gallin J I 
Published: December 2022

Abstract
We describe a 15-yr-old girl with recurrent bacterial infections who is refractory to the effects of LPS in vivo and in vitro and IL-1 in vitro. Intravenous challenge of the patient with Escherichia coli endotoxin caused a subnormal febrile response, little alteration in the number of circulating neutrophils, and subnormal elevations in the plasma levels of TNF-alpha, IL-6, IL-8, lactoferrin, and granulocyte CSF; however, normal levels of the anti-inflammatory mediators IL-1 receptor antagonist and soluble TNF receptor (60 kDa) were induced. Studies in vitro indicated the patient's monocytes expressed CD14, the LPS receptor, and bound LPS in a specific manner, but failed to produce TNF-alpha and granulocyte CSF after stimulation with LPS, and failed to respond to IL-1, heat-killed Staphylococcus aureus, and soluble glucan. Peripheral blood patient neutrophils exhibited normal expression of CD14, but failed to respond to treatment with LPS (100-1000 ng/ml for 30 min at 37 degrees C), a treatment that caused increased expression of the surface markers, C10, CD18, CD11b, CD67, and CD45, and decreased expression of L-selectin in normal neutrophils. Treatment of normal and patient neutrophils with FMLP (0.1 microM) resulted in equivalent altered expression of these surface markers. Patient neutrophils could not be primed by either LPS or IL-1beta for enhanced FMLP-induced O2- generation, but primed normally to TNF-alpha and platelet-activating factor. This patient's hyporesponsiveness to LPS and IL-1 is most likely due to a defect very early in the signal-transduction pathway.
HIV-induced T cell syncytia are self-perpetuating and the primary cause of T cell death in culture.
Authors: Sylwester A , Murphy S , Shutt D , Soll D R 
Published: December 2022

Abstract
Prior studies suggested that induced fusion in T cell cultures infected with syncytium-inducing HIV was not the primary cause of T cell death. However, these studies failed to assess the contribution of fusion in terms of syncytium volume, rather than syncytium frequency. This question has been reassessed by monitoring the frequency, volume, rate of growth, longevity, p24 production, viral budding, and self-propagating ability of syncytia in HIV-infected SUP-T1 cell cultures and individually isolated syncytia seeded in uninfected SUP-T1 cell cultures. The results demonstrate that in these cultures syncytium formation is the principal mechanism of T cell death, syncytia are the main source of virus production, and both virus production and syncytium longevity are independent of syncytium size, but dependent on syncytium age, suggesting that both are programmed events.
Different developmental arrest points in RAG-2 -/- and SCID thymocytes on two genetic backgrounds: developmental choices and cell death mechanisms before TCR gene rearrangement.
Authors: Diamond R A , Ward S B , Owada-Makabe K , Wang H , Rothenberg E V 
Published: December 2022

Abstract
To analyze the early development of T cell precursors in the absence of TCR gene rearrangement, recombinase-activating gene-deficient (RAG-2 -/-) thymocytes were compared with thymocytes from SCID mice on the C.B-17 (BALB) and B6 genetic backgrounds. RAG-2 -/- thymocytes accumulate as quiescent cells with a heat-stable Ag (HSA)-positive CD25+ CD44- c-kit(low) phenotype, resembling normal cells just before selection for functional TCR beta-chain expression. CD44 and c-kit progressively down-regulate in the HSA+ subset, providing a background-independent and TCR-independent developmental clock. On this basis, compared with RAG-2 -/- thymocytes, SCID thymocytes 1) arrest at more heterogeneous, and generally earlier, stages; 2) accumulate to lower overall cell numbers; and 3) maintain higher populations of cycling and activated G1 cells, showing both increased responsiveness and increased cell death. B6-SCID thymocytes appear to die particularly early. Low levels of Fas were observed on "advanced" HSA+ SCID thymocytes but not on any RAG-2 -/- thymocytes, suggesting a potential difference in activation state or mechanism of death. In both RAG-2 -/- and SCID thymocytes, there are also two discrete subsets of HSA(low) CD25- CD44+ c-kit+ cells: a Sca-1+ CD44++ CD122- NK1.1- putative progenitor subset and an NK-like Sca-1- CD44+(+) CD122+ NK1.1+ subset. The absolute cell numbers in these HSA(low) subsets and the extent of NK cell differentiation, measured by perforin expression, are nearly constant in all the mutant strains analyzed, in contrast to the HSA+ CD25+ population, which was expanded in the RAG-2 -/-. Thus, the SCID thymocytes appear to undergo a normal generation but a premature death as compared with the RAG-2 -/- thymocytes.
Lck is necessary and sufficient for Fas-ligand expression and apoptotic cell death in mature cycling T cells.
Authors: Gonzalez-Garcia A , R-Borlado L , Leonardo E , Merida I , Martinez-A C , Carrera A C 
Published: December 2022

Abstract
Apoptotic cell death is induced in mature cycling T cells upon ligation of the Ag-specific TCR. This process is essential for the maintenance of homeostasis in the immune system, as it is capable of down-regulating ongoing immune responses. The analysis of the mechanism underlying TCR-induced programmed cell death has focused the attention of many scientists recently. In this regard, several recent reports have implicated Fas/Fas-ligand molecules as the final mediators of this process. Several other gene products have been implicated in the control of apoptosis (as Bcl-2, p53, and c-Myc); however, no information was available in the early signaling molecules that trigger this phenomena. The results presented in this work indicate that pp56(lck) src family kinase is actually required for the TCR to trigger cell death in mature cycling T cells. In fact, while inhibition of pp56(lck) expression with antisense oligonucleotides blocked TCR-induced apoptosis, pharmacologic inhibition of phosphatidylinositol 3-kinase activity had no effect. Accordingly, ligation of the Ag receptor in a cell line defective for pp56(lck) expression was unable to induce apoptosis, although it induced cellular stimulation, as measured by the expression of CD69. In addition, we show in this work that expression of constitutively active pp56(lck) mutants, but not pp59(fyn) mutants, in the absence of any other TCR-derived signal, is sufficient to induce apoptosis not only in transformed, but also in normal cycling T cells. Finally, evidence is presented indicating that a mechanism through which pp56(lck) regulates TCR-induced apoptosis in mature cycling T cells is by controlling Fas-ligand expression.
CD8Tc1 and Tc2 cells secrete distinct cytokine patterns in vitro and in vivo but induce similar inflammatory reactions.
Authors: Li L , Sad S , Kägi D , Mosmann T R 
Published: December 2022

Abstract
Naive CD8 T cells, similar to CD4 T cells, can differentiate into at least two subsets of cytolytic effector cells with distinct cytokine patterns: T cytotoxic-1 (Tc1) cells secrete a Th1-like cytokine pattern, including IL-2 and IFN-gamma; and Tc2 cells produce Th2 cytokines, including IL-4, IL-5, and IL-10. As CD4 Th1 cells induce delayed-type hypersensitivity (DTH) more effectively than Th2 cells, we tested the potential ability of Tc1 and Tc2 cells to induce DTH. Allospecific Tc1 or Tc2 cells were injected into the footpads of naive mice expressing the target Ag. Tc1 and Tc2 cells induced comparable levels of Ag-specific footpad swelling with similar kinetics. They also induced similar levels of footpad edema and similar infiltration of macrophages and neutrophils. However, Tc2 cells induced slightly more eosinophil infiltration. Analysis of footpad extracts showed that Tc1 and Tc2 cells retained their distinct in vitro cytokine profiles in the injected footpads. These results suggest that both Tc1 and Tc2 cytokines can be associated with the DTH reaction induced by CD8 T cells. Perforin-deficient Tc1 or Tc2 cells also induced DTH, although at lower levels, suggesting that perforin-mediated cytotoxicity of CD8 T cells is not essential for CD8-induced DTH. Thus, despite their distinct cytokine profiles in vitro and in vivo, Tc1 and Tc2 cells induce similar DTH reactions.
Antigen-specific B cells preferentially induce CD4+ T cells to produce IL-4.
Authors: Macaulay A E , DeKruyff R H , Goodnow C C , Umetsu D T 
Published: December 2022

Abstract
The role of Ag presentation by B cells in regulating the development of T cells with restricted cytokine profiles remains controversial. In this report, we compared Ag presentation by naive polyclonal B cells, naive Ag-specific B cells (from Ig receptor transgenic mice), or splenic adherent cells (SAC) and examined the capacity of these cells to influence cytokine production by CD4+ T cells. Freshly isolated naive B cells stimulated vigorous T cell proliferation and very strong T cell cytokine responses, but only when cultured with Ag recognized by the B cell Ig receptor (cognate Ag) and not when cultured with a noncognate Ag. Under these conditions, B cells activated by Ig receptor-mediated endocytosis of Ag induced both naive and Ag-primed CD4+ T cells to produce high levels of IL-4 (300-4000 pg/ml). In contrast, SAC induced the production of very low levels of IL-4 (&lt;100 pg/ml) but much higher maximal levels of IFN-gamma than did Ag-specific B cells. The induction of IL-4 synthesis by Ag-specific B cells was significantly reduced by blocking CD40-CD40 ligand (CD40L) interactions or by the addition of small quantities of rIL-12. These results suggest that B cells activated by their cognate Ag preferentially induce IL-4 synthesis as a result of the interaction of CD40L on T cells with CD40, whereas SAC preferentially induce IFN-gamma synthesis by T cells as a result of their greater production of IL-12 and their limited capacity to trigger CD40L on T cells.
Differential expression of the beta2-adrenergic receptor by Th1 and Th2 clones: implications for cytokine production and B cell help.
Authors: Sanders V M , Baker R A , Ramer-Quinn D S , Kasprowicz D J , Fuchs B A , Street N E 
Published: December 2022

Abstract
An important function of the sympathetic nervous system is to maintain homeostasis by modulating the level of cellular activity in many diverse organ systems. The sympathetic neurotransmitter norepinephrine modulates the level of T and B lymphocyte activity by binding to the beta2-adrenergic receptor (beta2AR). The present study was designed to elucidate the mechanism by which stimulation of the beta2AR affects both Th1/Th2 cell cytokine production and Th1/Th2 cell-dependent Ab production. Clones of murine Th1/Th2 cells were exposed to the beta2AR agonist terbutaline before activation by Ag-presenting B cells. Terbutaline exposure of Th1 cells before activation inhibited IFN-gamma production by Th1 cells and subsequent IgG2a production by B cells. IgG2a inhibition was prevented by addition of the betaAR antagonist nadolol or exogenous IFN-gamma. In contrast to Th1 cells, terbutaline did not affect either IL-4 production by Th2 cells or subsequent IgG1 production by B cells. Although baseline levels of intracellular cAMP were similar in both subsets, terbutaline induced an increase in cAMP levels in Th1 cells only. Radioligand binding studies showed that a detectable number of beta2AR binding sites were present on Th1 cells, but not on Th2 cells. Immunofluorescence analyses showed that Th1 cells expressed a higher level of the beta2AR cytoplasmic carboxyl terminus than did Th2 cells. These results show that expression of the beta2AR binding site by Th1 cells, but not by Th2 cells, establishes a physiologic mechanism for selective modulation of Th1 cell IFN-gamma production and IFN-gamma-dependent IgG2a production, provided that beta2AR stimulation occurs before cell activation by a B cell.
Bone marrow-derived dendritic cells can process bacteria for MHC-I and MHC-II presentation to T cells.
Authors: Svensson M , Stockinger B , Wick M J 
Published: December 2022

Abstract
Dendritic cells can engulf particulate Ags and induce T cell proliferative responses after pulsing with particulate Ag. However, their capacity to process viable Gram-negative bacteria for presentation by MHC-I and MHC-II has not been shown. We therefore characterized the ability of murine bone marrow-derived dendritic cells to process Escherichia coli and Salmonella typhimurium, expressing defined epitopes for presentation by MHC-I and MHC-II molecules. The I-Ak-restricted 46-61 epitope from hen egg white lysozyme (HEL(46-61)) or the Kb-restricted 257-264 epitope from chicken egg OVA (OVA(257-264)) was expressed as fusion proteins in the bacterial cytoplasm as the Crl-HEL and Crl-OVA fusion proteins, respectively. Bacteria expressing Crl-HEL or Crl-OVA, or beads coated with HEL or OVA, were coincubated with murine bone marrow-derived dendritic cells, and Ag processing and presentation were quantitated using T cell hybridomas. The data show that granulocyte-macrophage CSF-stimulated dendritic cells can process live intact Gram-negative bacteria for peptide presentation by MHC-I and MHC-II. Cytochalasin D inhibition studies revealed that processing for both MHC-I and MHC-II presentation required cytoskeletal rearrangements. Processing for MHC-I and MHC-II presentation was inhibited by ammonium chloride, suggesting that acidic compartments were required. Thus, granulocyte-macrophage CSF-stimulated murine bone marrow dendritic cells are capable of processing exogenous particulate Ags, including bacteria with no known mechanism for phagosomal escape, for peptide presentation by both MHC-I and MHC-II. These data suggest that dendritic cells may be important in priming both CD4+ and CD8+ T cells to bacterial Ags.
A CD8 genomic fragment that directs subset-specific expression of CD8 in transgenic mice.
Authors: Hostert A , Tolaini M , Festenstein R , McNeill L , Malissen B , Williams O , Zamoyska R , Kioussis D 
Published: December 2022

Abstract
Helper and cytotoxic T cell subsets require the expression of different coreceptors (CD4 and CD8, respectively) for their development and function. We have cloned the CD8 gene locus from genomic cosmid and P1 libraries and analyzed the region around the CD8alpha and CD8beta genes for gene expression regulatory elements. DNase I (DNase I) hypersensitivity analysis of 80 kb in the CD8 locus identified four clusters of putative regulatory regions, three of which are thymocyte specific. Transgenic mice carrying the cloned CD8alphabeta genomic locus and containing the identified DNase I-hypersensitive site clusters express the transgenic CD8 in a developmentally regulated, tissue-specific, and CD8 T cell subset-specific manner.
Differential recruitment of leukocyte populations and alteration of airway hyperreactivity by C-C family chemokines in allergic airway inflammation.
Authors: Lukacs N W , Strieter R M , Warmington K , Lincoln P , Chensue S W , Kunkel S L 
Published: December 2022

Abstract
Allergic airway inflammation is characterized by peribronchial leukocyte accumulation within the airway. Subsequent tissue damage leading to airway hyperreactivity is a result of activation of multiple leukocyte populations. Using an established model of allergic airway inflammation induced by intratracheal challenge with parasite (Schistosoma mansoni) egg Ag in presensitized mice, we have examined differential leukocyte recruitment. These studies have identified key chemokines involved in the accumulation of specific subsets of cells and the induction of airway hyperreactivity. In this study we have examined three C-C family chemokines, MCP-1, MIP-1alpha, and RANTES, which promote mononuclear cell- and eosinophil-specific recruitment to the airway. The in vivo neutralization of either MIP-1alpha or RANTES, but not MCP-1, significantly reduced the intensity of the eosinophil recruitment to the lung and airway during the allergic airway response by &gt;50 and &gt;60%, respectively. In contrast, neutralization of MCP-1 significantly reduced total leukocyte migration (&gt;50% reduction), whereas neutralization of RANTES and MIP-1alpha had no significant affect on the overall leukocyte migration. Further examination of the effect of MCP-1 depletion indicated that both CD4+ and CD8+ lymphocyte subsets were decreased. Depletion of MCP-1 significantly reduced the airway hyperreactivity to near control levels, whereas depletion of MIP-1alpha or RANTES did not affect the intensity of airway hyperreactivity. These data indicate that multiple C-C chemokines are involved in the recruitment of particular leukocyte populations and that neutralization of MCP-1, but not RANTES or MIP-1alpha, significantly reduced airway hyperreactivity.