bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutral proteinases of human mononuclear phagocytes. Cellular differentiation markedly alters cell phenotype for serine proteinases, metalloproteinases, and tissue inhibitor of metalloproteinases.
Authors: Campbell E J , Cury J D , Shapiro S D , Goldberg G I , Welgus H G 
Published: December 2022

Abstract
Mononuclear phagocytes have the capacity to directly participate in extracellular matrix turnover via secretion of neutral proteinases. We have studied the effects of in vivo and in vitro differentiation upon cellular content or secretion of a spectrum of neutral proteinases, along with a counter-regulatory metalloproteinase inhibitor (TIMP). We found 1) matrix-degradative serine proteinases (leukocyte elastase and cathepsin G) were lost during cellular maturation and/or differentiation; 2) the 92-kDa type IV/type V collagenase and TIMP were secreted earliest in mononuclear phagocyte differentiation, whereas stromelysin secretion was observed only by LPS-stimulated alveolar macrophages; 3) exposure of alveolar macrophages, but not monocytes, to phorbol esters and LPS resulted in markedly augmented secretion of all studied metalloproteinases and TIMP; 4) monocyte-derived macrophages partially (but not completely) mimicked the metalloproteinase secretory phenotype of alveolar macrophages; and 5) the secretory phenotype of alveolar macrophages for interstitial collagenase (but not TIMP) was largely lost during in vitro culture. These results underscore the complexity of the process of differentiation in human mononuclear phagocytes, and provide insights into the variable capacity of mononuclear phagocytes to degrade extracellular matrix components. Moreover, we anticipate that human mononuclear phagocytes at various stages of differentiation will provide a useful model system for study of the variable regulation of secretion of human matrix-degrading metalloproteinases.
Graded G-protein uncoupling by pertussis toxin treatment of human polymorphonuclear leukocytes.
Authors: Omann G M , Porasik-Lowes M M 
Published: December 2022

Abstract
Pertussis toxin (PT) inhibits polymorphonuclear leukocyte (PMN) function by ADP-ribosylating and inactivating guanine nucleotide binding proteins (G-proteins) that transduce activation by chemoattractants such as N-formyl peptides (FP). Studies of PMN activation during the time course of PT treatment yielded these results. 1) Responses were differentiated based on their sensitivity to PT treatment. Suboptimal PT treatment that resulted in 50% inhibition of the FP-induced actin-associated right angle light scatter response resulted in greater than 90% inhibition of oxidant production. Exhaustive PT treatment was required to completely inhibit the right angle light scatter response. This is consistent with previous observations that, relative to oxidant production, actin polymerization requires 100-fold fewer active N-formylpeptide receptors to elicit the response. This differential sensitivity to PT treatment has important implications for studies that use pertussis toxin to determine if the neutrophil G-protein is involved in the signaling of responses. If inhibition of oxidant production is used as the only indicator of the effectiveness of PT treatment, significant cytoskeletal changes may still be activated in these cells. Inhibition of actin polymerization is a much more rigorous indicator of complete G-protein inhibition by PT. 2) Analysis of FP-induced actin polymerization and cytosolic calcium elevation using flow cytometry, which measures individual cell responses, revealed that PT treatment resulted in the conversion of PMN from a responding to a non-responding population. In contrast, in control PMN, submaximal doses of FP caused submaximal stimulation of all the cells. The all-or-none effect of PT may result from heterogeneous insertion of the A-promoter of PT into the cell or it may result from a sharp threshold of coupled G-proteins required to transduce the responses.
Functional heterogeneity among herpes simplex virus-specific human CD4+ T cells.
Authors: Yasukawa M , Inatsuki A , Horiuchi T , Kobayashi Y 
Published: December 2022

Abstract
One hundred thirteen HSV-specific CD4+ T cell clones were established from the PBL of a healthy person and their functional heterogeneity was investigated. All clones proliferated in response to stimulation with HSV in the presence of autologous APC. Among those, 48 clones showed cytotoxic activity to HSV-infected autologous EBV-transformed lymphoblastoid cell line, but not to HSV-infected autologous fibroblasts, HSV-infected allogeneic cells, or K562 cells (group 1). Five clones showed cytotoxicity against HSV-infected autologous cells as well as HSV-infected allogeneic cells and K562 cells (group 2). The cytotoxicity of these clones was found to be mediated by the direct killing but not by the "innocent bystander" killing of target cells. Sixty clones showed no cytotoxic activity, however, among these, 23 revealed HLA-unrestricted and nonspecific cytotoxicity in the presence of PHA in culture (group 3), and the remaining 37 did not show any cytotoxic activity even in the presence of PHA (group 4). The cytotoxic patterns of these clones did not change in activated and resting phases, suggesting that the difference in cytotoxic ability does not depend on cell cycles. The cytotoxic activity of group 1 was inhibited by addition of anti-HLA-DR or anti-CD3 mAb to the culture, whereas these mAb had no effect on the cytotoxicity of group 2. All four groups of clones had helper activity for anti-HSV antibody production by autologous B cells. Moreover it was found that all groups of clones simultaneously produced IL-2, IL-4, and IFN-gamma after culture with APC followed by HSV Ag stimulation. The surface phenotype of all clones was uniformly CD2+, CD3+, CD4+, CD8-, CD29+, CD45RA-, but expression of Leu 8 was varied. These data therefore indicate that HSV-specific human CD4+ T cells are classified into at least four groups according to the presence and specificity of cytotoxicity, i.e., Th cells with HSV-specific and HLA-class II-restricted cytotoxicity, Th cells with HLA-unrestricted and nonspecific cytotoxicity, Th cells with lectin-dependent cytotoxicity, and Th cells without cytotoxic activity. The present finding of functional heterogeneity among virus-specific human CD4+ T cells might shed light on the pathogenesis of CD4+ T cell immunodeficiency, such as human retrovirus infections.
Involvement of two distinct regulatory T cell populations in the antigen-specific suppression of cytolytic T cell generation.
Authors: Devens B H , Koontz A W , Kapp J A , Pierce C W , Webb D R 
Published: December 2022

Abstract
Alloantigen-specific, radiation-resistant T cells generated in mixed-lymphocyte cultures inhibited the generation of allospecific CTL responses in vitro. This regulatory T cell population was studied using mAb generated to Ag-specific suppressor factors that regulate the response to the synthetic terpolymer L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT). Both monoclonal 984 D4.6.5 and a pool of four mAb 2441, when added in the presence of complement, eliminated alloantigen-specific inhibition of the CTL response. When separate cell cultures treated with mAb 984 or 2441 plus complement were recombined, inhibition was reestablished, suggesting that two or more populations of cells are required for active inhibition. Furthermore, neither the mAb 984 nor the mAb 2441 plus complement had any effect on any stage of CTL development. This suggests that the inhibition of the CTL response was not the result of cytolytic activity via the regulatory T cells. Experiments in which these antibodies were added without complement treatment showed that the mAb 2441 neutralized the inhibitory activity, whereas mAb 984 augmented inhibition. It is concluded from these studies that regulatory T cells originally identified in humoral immune responses also regulate cell-mediated immune responses. Suppressor epitopes are displayed on the surface of these cells that allow them to be distinguished from other T cells. These data also show the utility of the mAb 984 and 2441 raised against specific suppressor T cell products in different experimental models of immunity. These studies suggest that phenotypically distinct Ts cell populations can play a normal regulatory role in both cell-mediated and humoral immunity.
Demonstration of the origin of human mast cells from CD34+ bone marrow progenitor cells.
Authors: Kirshenbaum A S , Kessler S W , Goff J P , Metcalfe D D 
Published: December 2022

Abstract
It has been established that murine mast cells are derived from a pluripotent bone marrow stem cell. In humans, the corresponding pluripotent cell is included in the CD34+ bone marrow population. To determine whether human mast cells arise from CD34+ human progenitor cells, enriched CD34+ cells were cultured over agarose surfaces (interphase cultures) or cocultured with mouse 3T3 fibroblasts in the presence of recombinant human (rh) IL-3. The presence of both mast cells and basophils was determined using a variety of histochemical and immunohistologic techniques, including immunogold labeling for IgE receptors and mast cell tryptase. Mast cells and basophils continued to appear in cultures when T cell, B cell, macrophage, and eosinophil committed progenitor cells were removed, but were not seen in cultures from which CD34+ cells were removed. CD34+ cells layered over agarose in the presence of rhIL-3 were shown to give rise to cultures that contained mast cells (1 to 5%) and basophils (25 to 40%). Cultures supplemented with rhIL-4 showed no additional increase in mast cells or basophils. CD34+ cells cocultured with 3T3 fibroblasts in the presence of rhIL-3 gave rise to mast cells within the fibroblast monolayer, which by 6 wk comprised up to 46% of the monolayer. CD34-cells on 3T3 fibroblasts gave rise to few mast cells (2% of the monolayer). Mast cell granules from interphase cultures contained homogeneous electron-dense material. In contrast, mast cells within 3T3 monolayers at 6 wk contained a variety of granule morphologies, including scroll, mixed, reticular, dense core, or homogeneous patterns. We conclude that both human mast cells and basophils arise from CD34+ human progenitor cells.
Signaling through surface IgM in tolerance-susceptible immature murine B lymphocytes. Developmentally regulated differences in transmembrane signaling in splenic B cells from adult and neonatal mice.
Authors: Yellen A J , Glenn W , Sukhatme V P , Cao X M , Monroe J G 
Published: December 2022

Abstract
During the course of B lymphocyte development, newly emerging surface Ig+ B cells pass through a stage when Ag-Ag receptor interactions lead not to immune responsiveness but to a state of functional tolerance. We have explored the molecular basis of antigenic nonresponsiveness and tolerance susceptibility using tolerance-susceptible surface Ig+ splenic B lymphocytes from neonatal mice and anti-mu chain antibodies as a polyclonal ligand. In this population of cells, surface IgM is uncoupled from the inositol phospholipid (PI)-hydrolysis pathway at a point proximal to the receptor; anti-mu antibodies did not stimulate inositol phosphate generation despite the fact that PI-hydrolysis was observed after treatment with A1F4, implicating the existence of a functional G protein and phospholipase C. Further evidence for a difference early in the signal transduction pathway stems from the finding that anti-mu stimulation does not induce the expression of two immediate/early PKC-linked genes egr-1 and c-fos. This appears to be the primary signaling difference between the mature and immature B cells from the neonatal mouse splenic population, as these cells undergo a G0-G1 cell cycle phase transition when surface IgM is bypassed using phorbol diester and calcium ionophore. Interestingly, despite undetectable levels of PI-hydrolysis, we observed equivalent receptor-mediated changes in intracellular calcium when comparing the immature and mature populations. These results indicate incomplete coupling of surface IgM to the signal transduction machinery operative in mature, immunocompetent B cells and suggests a molecular mechanism accounting for the differential processing of surface IgM signals into activation vs tolerogenic responses observed in these two stages of B cell development.
Frequency analysis of IgE-secreting B lymphocytes in persons with normal or elevated serum IgE levels.
Authors: King C L , Poindexter R W , Ragunathan J , Fleisher T A , Ottesen E A , Nutman T B 
Published: December 2022

Abstract
The immunoregulatory mechanisms that determine the high serum IgE antibody levels in disorders such as helminth parasite infections and the hyper-IgE recurrent infection syndrome (HIE) remain poorly understood. To assess whether elevated serum IgE levels result from an increased number of B lymphocytes committed to IgE production, the proportion of IgE-producing B lymphocytes was determined by a filter immunoplaque assay using PBMC from persons with a broad range of serum IgE levels that included normal persons (n = 9) and patients with loiasis (n = 12), tropical pulmonary eosinophilia (TPE) (n = 6), lymphatic filariasis (n = 28), and HIE (n = 8). PBMC from these persons were assessed for production of in vitro IgE. The geometric mean number of IgE-secreting cells in 10(5) B lymphocytes in PBMC was 0.42 (range 0-2.2) in normal persons, 5.6 (range 0.1-35.5) among patients with loiasis, 9.4 (range 0-53.2) among patients with lymphatic filariasis, 52 (range 31.5-115) among patients with TPE, and 218 (range 56-1404) among patients with HIE. When all study subjects were grouped, there were significant correlations with serum IgE levels (r2 = 0.78; p less than 0.0001) and net spontaneous in vitro IgE production (r2 = 0.8; p less than 0.0001). Estimates of the amount of IgE production per B lymphocyte were similar among normal persons, patients with filarial infections, and patients with TPE (geometric means of 134, 96, and 141 pg/ml/cell, respectively); in contrast, for HIE patients, IgE production by individual B cells was significantly lower (geometric mean 28 pg/ml/cell; p less than 0.001). These observations demonstrate that clonal expansion of IgE-producing B lymphocytes is a major mechanism underlying the elevated serum IgE levels seen in persons with hyper-IgE states.
Generation and cloning of stable human IgE-secreting cells that have rearranged the C epsilon gene.
Authors: Thyphronitis G , Max E E , Finkelman F D 
Published: December 2022

Abstract
Although the secretion of Ig isotypes other than IgM is generally accompanied by a DNA rearrangement that deletes C mu (and the other IgCH genes located between VDJ and the expressed CH gene), a system has recently been described that generates a high frequency of IgE-secreting cells that have failed to delete IgCH genes or to rearrange their C epsilon genes. These cells, derived from EBV-transformed human PBMC, secrete IgM and IgD as well as IgE. To determine whether the absence of C epsilon rearrangement and CH gene deletion is a general phenomenon for human IgE-secreting cells, we have characterized IgE-secreting cells that are generated by culturing purified human B cells with EBV plus IL-4 in the presence of irradiated human PBMC. In contrast to the earlier observation, we have not been able to detect any cells that demonstrate cytoplasmic staining for IgE and concurrently stain for a second Ig isotype. Stable IgE-secreting cell lines and clones produced by this method have rearranged one of their C epsilon genes and have deleted both C mu genes. These observations demonstrate that the generation of human IgE-secreting cells can involve the same gene rearrangement and deletional mechanisms that lead to the generation of cells that secrete other isotypes.
IL-1 induces ornithine decarboxylase in normal T lymphocytes.
Authors: Bristol L A , Smith M R , Bhat N K , Durum S K 
Published: December 2022

Abstract
IL-1 alpha regulation of ornithine decarboxylase (ODC) was examined in T cells because IL-1 is a costimulus for T cell proliferation and ODC is a critical enzyme in the metabolic events associated with cellular proliferation. In the present study, we demonstrate that IL-1 alpha induces ODC mRNA and ODC enzyme activity in T cells. Unlike many IL-1 actions on T cells, this did not require a costimulus from the TCR, IL-1 alone being sufficient to induce ODC. The mechanism of IL-1 induction of ODC probably operates at several levels, including transcription, mRNA stability, and translation. Previous studies have shown that IL-1 prepares T cells for replication by increasing the production of c-jun, c-fos, c-myc, growth factors, growth factor receptors, and the response to growth factors. From the present study, ODC induction can be added to the list of IL-1-induced replicative machinery in T cells.
Priming with T helper cell epitope peptides enhances the antibody response to the envelope glycoprotein of HIV-1 in primates.
Authors: Hosmalin A , Nara P L , Zweig M , Lerche N W , Cease K B , Gard E A , Markham P D , Putney S D , Daniel M D , Desrosiers R C 
Published: December 2022

Abstract
The induction of a memory immune response to HIV, mediated by any kind of effector mechanism, requires the induction of T cell help. In previous studies performed in different murine MHC haplotypes, three immunodominant T cell epitopes (T1, T2, and TH4.1) had been identified in the HIV envelope glycoprotein. Moreover, these peptides were proliferative T cell epitopes in humans. In this study, rhesus monkeys, Macaca mulatta, were primed with these three peptides either in combination or given separately. Half of the monkeys had a proliferative response to one or more of the priming peptide(s). Those monkeys who had a T cell proliferative response also had a high antibody response after one boost with a suboptimal dose of the native protein gp 160, whereas three of four control monkeys who had received only the native protein immunization gave no detectable antibody response, and one displayed a very weak response. For reasons that are unclear, antibodies only to the gp41 portion of gp 160 could be detected in the sera. Thus, the peptides can prime Th cells in primates for an enhanced antibody response on first exposure to the whole protein. The three peptides belong to highly conserved and nonglycosylated regions of the envelope protein. The fact that the peptides acted as immunogenic T cell proliferative and helper epitopes in nonhuman primates is very encouraging for including them in future vaccine studies in humans.
T cell epitopes of the circumsporozoite protein of Plasmodium vivax. Recognition by lymphocytes of a sporozoite-immunized chimpanzee.
Authors: Nardin E , Clavijo P , Mons B , van Belkum A , Ponnudurai T , Nussenzweig R S 
Published: December 2022

Abstract
The humoral and cellular antisporozoite immune responses of a laboratory-born chimpanzee were measured following multiple exposures to the bites of Plasmodium vivax-infected mosquitoes. T cell lines and clones derived from the chimpanzee's PBL were used to identify T cell epitopes of the P. vivax circumsporozoite (CS) protein. Two independently obtained cell lines, established by culturing the PBL with either a recombinant P. vivax circumsporozoite (rPvCS) protein or a pool of synthetic peptides spanning the rPvCS sequence, recognized a 20-mer peptide from a nonpolymorphic region of the carboxyl terminus of the CS protein. This peptide overlaps a sequence homologous to region II of the Plasmodium falciparum CS protein. A third T cell line recognized an epitope within the central repeat domain, which has recently been found to be a polymorphic region of the P. vivax CS protein. The CD4+ clones derived from this third T cell line secreted IFN-gamma and IL-2 when stimulated with either the P. vivax repeat peptide (DRAAGQPAG)2 or the rPvCS protein.
Cross-linking of surface Ig receptors on murine B lymphocytes stimulates the expression of nuclear tetradecanoyl phorbol acetate-response element-binding proteins.
Authors: Chiles T C , Liu J L , Rothstein T L 
Published: December 2022

Abstract
Cross-linking of sIg on primary B lymphocytes leads to increased nuclear DNA-binding activity specific for the tetradecanoyl phorbol acetate-response element (TRE), as judged by gel mobility shift assays. Stimulation of B cells to enter S phase of the cell cycle by treatment with the combination of phorbol ester plus calcium ionophore also stimulated nuclear TRE-binding activity within 2 h, with maximal expression at 4 h; however, phorbol ester and calcium ionophore were not as effective in stimulating binding activity when examined separately. Stimulated nuclear expression of TRE-binding activity appears to require protein synthesis. Fos- and Jun/AP-1-related proteins participate directly in the identified nucleoprotein complex, as shown by the ability of c-fos- and c-jun-specific antisera to either alter or completely abolish electrophoretic migration of the complex in native gels. Further, UV photo-cross-linking studies identified two major TRE-binding protein species, whose sizes correspond to TRE-binding proteins derived from HeLa cell nuclear extracts. The results suggest that in primary B cells nuclear TRE-binding activity represents a "downstream" signaling event that occurs subsequent to changes in protein kinase C activity and intracellular Ca2+ but that can be triggered "physiologically" through sIg.
Murine Th1 and Th2 clones proliferate optimally in response to distinct antigen-presenting cell populations.
Authors: Gajewski T F , Pinnas M , Wong T , Fitch F W 
Published: December 2022

Abstract
We recently have devised a method for the derivation of OVA-specific Th1 and Th2 clones from the same primed lymph node cell preparation. Using a panel of such cells, we have examined the ability of distinct APC populations to stimulate proliferation of Th1 and Th2 clones. Both subsets proliferated well in response to OVA in the presence of whole spleen cells. However, purified B cells stimulated optimal proliferation of Th2 clones, whereas adherent cells stimulated optimal proliferation of Th1 clones. The proliferative response of Th2 cells stimulated with spleen cells irradiated with 3300 rad was dramatically less than that observed in response to spleen cells treated with 1000 rad; Th1 clones responded similarly to spleen cells exposed to either irradiation dose. Differential activation of Th1 and Th2 clones did not correlate with MHC-restricting element, or susceptibility to inhibition by mAb directed against CD4 or LFA-1. Lymphokine production by each subset still occurred under conditions of suboptimal proliferation, suggesting that the appropriate Ag processing and presentation events had transpired. The same pattern of response was observed using a specific OVA peptide that does not require processing, suggesting that differential responsiveness of Th1 and Th2 clones to different APC populations is not a result of defective Ag processing. Neither rIL-1 nor rIL-6 restored optimal proliferation of either subset. Our results suggest that unique cofactors are necessary for the optimal proliferation of Th1 and Th2 clones, and that these cofactors are produced by specialized APC populations.