bluuebunny/crossref_metadata_2025_split huggingface dataset:
Divergent transforming growth factor-beta effects on IL-6 regulation of acute phase plasma proteins in rat hepatoma cells.
Authors: Campos S P , Wang Y , Koj A , Baumann H 
Published: December 2022

Abstract
The rat hepatoma cell line, H-35, responds to IL-1- and IL-6-type cytokines by an increased transcription of specific acute phase plasma protein (APP) genes. Transforming growth factor-beta (TGF-beta), although ineffective on its own in regulating APP genes, modulates the action of the IL-type cytokines. In growing cultures, the IL-6 and IL-11 stimulation of thiostatin and hemopexin is enhanced by TGF-beta, whereas the stimulation of other APP is reduced. The effects of leukemia inhibitory factor, ciliary neurotrophic factor, IL-1, and TNF-alpha are generally attenuated by TGF-beta. Enhancement by TGF-beta of the IL-6-induced response can be explained in part by the fact that TGF-beta, in combination with dexamethasone, stimulates severalfold the expression of the 80-kDa ligand-binding subunit of IL-6R. Serum deprivation of H-35 cells for 3 days leads to an enhanced basal and cytokine-stimulated level of APP gene expression concomitant with a loss of the divergent regulatory effect of TGF-beta. In growth-arrested H-35 cells, TGF-beta still enhances the IL-6R expression but it attenuates all IL-6 effects on APP genes. These data suggest that TGF-beta influences the signal transduction of the IL-type cytokines by separate mechanisms and that the manifestation of the TGF-beta action is modulated by the growth state of the cell culture.
Suramin inhibits the stimulation of acute phase plasma protein genes by IL-6-type cytokines in rat hepatoma cells.
Authors: Baumann H , Strassmann G 
Published: December 2022

Abstract
The cytokines, IL-1 beta, TNF-alpha, IL-6, IL-11, leukemia inhibitory factor, and ciliary neurotrophic factor, stimulate the expression of specific sets of acute phase plasma proteins in the rat hepatoma H-35 cell line. In this paper, the experimental drug suramin is shown to inhibit in a dose-dependent fashion the cell response to these cytokines, with the exception of TNF-alpha. The action of the IL-6-type cytokines is more sensitive to suramin inhibition that that of IL-1 beta. The effect of suramin is detectable within 30 min at the level of gene transcription and appears to be mediated by the impairment of receptor function and/or signal transduction, rather than by the inhibition of nucleic acid polymerases or DNA topoisomerase II. Similar analysis of human hepatoma HepG2 cells indicated a several-fold higher resistance to suramin and in inhibition that was less cytokine-specific than in H-35 cells. The data suggest that suramin has the potential not only to modulate the proliferation or differentiation of tumor cells as described previously, but also to affect a differentiated cell function. This broad pleiotropic action has to be taken into consideration when applying suramin as a therapeutic agent.
Regional specialization of the mucosal immune system. Intraepithelial lymphocytes of the large intestine have a different phenotype and function than those of the small intestine.
Authors: Camerini V , Panwala C , Kronenberg M 
Published: December 2022

Abstract
Intraepithelial lymphocytes (IEL) are found in both the small and the large intestine. We demonstrate that there are a number of striking phenotypic and functional differences between the two populations of IEL isolated from mice. In the large intestine, the majority of IEL express the alpha beta TCR, and among these TCR-alpha beta+ lymphocytes, CD4+ cells are as prevalent as CD8+ cells. In contrast, in the small intestine, most of the TCR-alpha beta+ IEL express CD8, and an increased percentage of cells express TCR-gamma delta. In addition, most TCR-gamma delta+ IEL isolated from the large intestine (LI-IEL) are CD4- CD8- cells, as compared to TCR-gamma delta+ IEL isolated from the small intestine (SI-IEL), which are predominantly CD8+. Furthermore, CD2 and the lymph node homing receptor, L-selectin, are expressed by most LI-IEL but not by SI-IEL. Furthermore, LI-IEL have much less cytolytic activity than SI-IEL. These data suggest that LI-IEL are a distinct population of lymphocytes that may have a different immunologic role than that of SI-IEL.
Wasting, ischemia, and lymphoid abnormalities in mice expressing T cell-targeted human tumor necrosis factor transgenes.
Authors: Probert L , Keffer J , Corbella P , Cazlaris H , Patsavoudi E , Stephens S , Kaslaris E , Kioussis D , Kollias G 
Published: December 2022

Abstract
To evaluate the biologic potential of T cell-specific TNF production in vivo, we have generated transgenic mice constitutively expressing TNF in their T cell compartment. This was achieved by placing a wild-type or a 3'-UTR modified fragment of the human TNF gene under the influence of the T cell-specific, locus control region of the human CD2 gene. Transgenic mice that express human TNF mRNA in T cells develop marked histologic and cellular changes locally in their lymphoid organs and a lethal wasting syndrome associated with widespread vascular thrombosis and tissue necrosis. The extent of pathologic changes and their time of onset appear to reflect levels of transgene expression. Thus, transgenic lines that express the transgene at high levels show both lymphoid organ and systemic abnormalities with wasting. In one transgenic line, mice express lower levels of the transgene and develop normally despite pronounced local lymphoid organ defects, confirming in vivo, the differential potential of localized and systemic TNF action. All pathologic changes could be neutralized by the administration of mAb specific for human TNF. These results demonstrate the important role of T cell-specific TNF production in the development of specific pathology and provide a means by which to evaluate the role of TNF in thymocyte development. Transgenic mice that express TNF constitutively in the T cell compartment offer a unique in vivo system by which to analyze the molecular character of systemic vs contact-dependent and paracrine modes of TNF action. Furthermore, given the species-specific nature of the mouse p75 TNF receptor, it is assumed that the pathology induced by human TNF in these transgenic mice is associated exclusively with p55 TNF receptor signaling. Conceivably, the differential contribution of each of the two TNF receptors in thymus development and TNF-mediated disease can be assessed by comparison of the biologic potential of human vs mouse TNF in the transgenic system developed.
Characterization of A1, a novel hemopoietic-specific early-response gene with sequence similarity to bcl-2.
Authors: Lin E Y , Orlofsky A , Berger M S , Prystowsky M B 
Published: December 2022

Abstract
Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates hemopoietic cell proliferation, differentiation, and functional activation by inducing the expression of specific genes. As part of an investigation of the regulation of gene expression by GM-CSF, we have previously identified a novel murine GM-CSF-inducible gene, A1. In this report, we present the complete nucleotide sequence of the A1 mRNA as well as a portion of the 5' flanking region, and describe the expression pattern of the gene. The results demonstrate that A1 is a hemopoietic tissue-specific gene that is expressed in several hemopoietic cell lineages, including T-helper lymphocytes, macrophages, and neutrophils. In murine bone marrow-derived macrophages, A1 gene expression is rapidly and transiently induced by GM-CSF, and the induction was independent of de novo protein synthesis. In addition to GM-CSF, a transient induction of A1 mRNA accumulation was observed in response to LPS in macrophages. This induction is not mediated by IL-1 alpha or IL-6, neither of which stimulate A1. In the myeloid precursor cell line, 32D cl3, A1 gene expression is stably induced during granulocyte colony-stimulating factor-stimulated myeloid cell differentiation. The A1 message encodes a predicted polypeptide with an M(r) of 20,024 and no signal peptide. The peptide sequence contains a region of 80 amino acids that shows similarity to bcl-2 and to the recently described bcl-2-related gene, MCL1. These data demonstrate that A1 is a novel early-response gene whose expression is associated with a variety of stimuli and occurs in several hemopoietic cell types.
Conserved T-cell receptor repertoire in simian immunodeficiency virus-infected rhesus monkeys.
Authors: Chen Z W , Kou Z C , Shen L , Reimann K A , Letvin N L 
Published: December 2022

Abstract
Studies to assess the possibility that the HIV may encode a superantigen that plays a role in the depletion of functional CD4+ lymphocytes in the infected individual have yielded discrepant results. The problem in performing conclusive examinations of this issue may be attributed, at least in part, to the difficulty of prospectively studying individuals from before their infection until the time of profound CD4+ lymphocyte loss. To determine whether the AIDS virus deletes particular subpopulations of V beta-expressing lymphocytes, we have employed an animal model of AIDS, the simian immunodeficiency virus (SIV)-infected macaque monkey. Rhesus monkeys were experimentally infected with SIVmac and studied prospectively. A PCR-based quantitative method for assessing TCR repertoire was employed to analyze the expression of 24 V beta and 30 V alpha gene families in the monkeys. Although circulating PBL were increased in number by 3 wk after SIVmac infection, the expanded lymphocyte populations exhibited no significant perturbation in their TCR V beta repertoires. PBL obtained from monkeys before and 0.5 to 3 years after infection displayed no significant change in V beta and V alpha gene family expression. Finally, no deletion of V beta-expressing cell subpopulations could be demonstrated in purified CD4+ lymphocytes from infected monkeys. This was true even for monkeys whose blood contained less than 200 CD4+ lymphocytes/microliters. These results indicate that the TCR repertoire is conserved in SIVmac-infected rhesus monkeys and suggests that mechanisms other than superantigen-induced deletion must be responsible for CD4+ lymphocyte loss in these animals.
Tissue-specific distribution and age-dependent increase of human CD11b+ T cells.
Authors: Hoshino T , Yamada A , Honda J , Imai Y , Nakao M , Inoue M , Sagawa K , Yokoyama M M , Oizumi K , Itoh K 
Published: December 2022

Abstract
Distribution of CD11b Ag, a member of the leukocyte integrin (beta 2 integrin) family, on human T cells is not well characterized. We investigated in this study the tissue distribution and age-related alteration of human CD11b+ T cells. Significant proportions of CD11b+ cells were found in T cells from adult peripheral blood (18-58 yr) (20%), liver (32%), and spleen (16%), but were rarely observed in those from thymus, lymph nodes, intraepithelial lymphocytes, lamina propria lymphocytes, and lung. In contrast, percentages of CD28+ T cells, a counter population of CD11b+ T cells, were highest in lymph nodes (91%), modest in intraepithelial lymphocytes (82%), lamina propria lymphocytes (77%), PBL (77%), spleen (73%) and lower in thymus (62%), lung (60%) and liver (56%). The CD11b+ T cells from peripheral blood gradually increased with age, whereas the CD28+ T cells showed an age-dependent decrease. Namely, the percentages of CD11b+ T cells were 6% in newborns (cord blood), 15% in young adults (18 to 22 yr), 25% in middleaged adults (45 to 58 yr), and 27% in aged adults (72 to 86 yr), whereas those of CD28+ T cells were 96%, 83%, 72%, and 71%, respectively. Proportions of CD11b+ T cells in TCR-gamma delta+ or CD8+ T cells were, respectively, higher than those in TCR-alpha beta+ or CD4+ T cells. Age-dependent increase of CD11b+ T cells in CD8+ T cells was more obvious than that of CD4+ T cells. Furthermore, CD11b+ CD28+ T cells increased in the peripheral blood only of aged adults. The percentage of CD11b+ CD28+ T cells in TCR-gamma delta+ T cells was highest in young adults (25%), whereas that in CD4+ T cells was highest in aged adults (15%). CD11b+ CD28+ T cells expressed much potent IFN-gamma, IL-2, and IL-4 at mRNA level than CD28+ CD11b- T cells or CD11b+ CD28- T cells, and had potential cytotoxic activity. Roles of CD11b+ T cells in vivo were discussed.
A monoclonal antibody capable of blocking the binding of Pf200 (MSA-1) to human erythrocytes and inhibiting the invasion of Plasmodium falciparum merozoites into human erythrocytes.
Authors: Su S , Sanadi A R , Ifon E , Davidson E A 
Published: December 2022

Abstract
Glycophorin A is a major receptor on human erythrocytes for Plasmodium falciparum, the human malaria parasite. In this work, we have produced four glycophorin A-specific mAb: 2B10, 1E4, 3H12, and 3H2. 2B10 was mapped to the amino terminal region of glycophorin (amino acids 1-31), and its binding to erythrocytes was fully dependent on sialic acid residues. 3H2 bound to the region close to the cell membrane, and its binding to Wr (b-) erythrocytes was significantly decreased, compared with its binding to Wr (b+) erythrocytes. 1E4 and 3H12 recognized sites between those identified by 2B10 and 3H2. Pf200 (MSA-1) is a surface protein on the P. falciparum merozoite which has been shown to bind to erythrocytes. By reciprocal inhibition assays, 2B10 and MSA-1 could be shown to share the same determinant on erythrocytes. Using an in vitro assay, we have shown that 2B10 was the most efficient inhibitor of the invasion of human erythrocytes by P. falciparum merozoites. We conclude that the binding site for MSA-1 is primarily located on the amino terminal region, amino acids 1-31, of glycophorin A, and that 2B10 is valuable for additional study of the interactions between P. falciparum merozoites and human erythrocytes.
IFN-gamma-induced recognition of the antigen-processing variant CMT.64 by cytolytic T cells can be replaced by sequential addition of beta 2 microglobulin and antigenic peptides.
Authors: Jefferies W A , Kolaitis G , Gabathuler R 
Published: December 2022

Abstract
The present study describes the functional nature of the MHC class I determinants expressed in CMT.64 cells and was undertaken to define and further analyze the deficiency in the cell line CMT.64 in the hope of elucidating the relative functional importance of constituent parameters in the recognition of these cells by CTL. We show that induction of Kb in CMT.64 cells with IFN-gamma results in molecules capable of presenting VSV epitopes to the appropriate CTL. However, cells untreated with IFN-gamma and infected with VSV are not recognized by VSV-specific CTL. This study reveals that beta 2 m3 is synthesized in limiting amounts in uninduced CMT.64 and becomes highly expressed after IFN-gamma induction. Thus, the limiting amount of beta 2 m expressed in uninduced cells may partially explain the inability of the cells to present viral components of CTL recognition. This concept is reinforced by the experiments identifying two functional effects upon the addition of immunogenic peptides to uninduced CMT.64 cells: at high peptide concentrations in excess of 5 nM, CMT.64 cells are recognized efficiently after 5 min of incubation; at the limiting peptide concentration of 500 pM, uninduced CMT.64 cells are only recognized providing beta 2m is added before or simultaneously with the antigenic peptide. BFA, an inhibitor of protein transport, and emetine, an inhibitor of protein synthesis, were used to show that at high peptide concentrations, 25 microM, recognition takes place after the peptide has stabilized the limited amount of newly arriving MHC/beta 2m complexes, devoid of peptides, at the cell surface of uninduced CMT.64 cells. These experiments thereby exclude the possibility that peptides are taken up into CMT.64 cells for assembly, transport and surface expression of functional MHC/beta 2m/peptide complexes. In summary, our data expands previous research showing the importance of exogenous beta 2m in sensitizing cells for CTL recognition with peptides added exogenously. These functional experiments also imply that the concentration of endogenous beta 2m may regulate the amount of MHC class I expressed at the cell surface and receptive to exogenous peptides. Finally, the phenotype of CMT.64 cells we describe provides evidence of the complexity of the Ag-presenting capacity of this cell line not previously identified in other studies on these cells, thus revising our understanding of the Ag-processing deficiency in these cells.
Stem cell factor induces mast cell adhesion to fibronectin.
Authors: Dastych J , Metcalfe D D 
Published: December 2022

Abstract
Stem cell factor (SCF) or c-kit ligand is a growth factor cytokine produced by stromal cells that is known to influence mast cell proliferation and differentiation. We hypothesized that SCF may also influence the adhesion of mast cells to connective tissue matrix. To examine this hypothesis, we stimulated MCP5/L mast cells or murine bone marrow-derived cultured mast cells (BMCMC) with either SCF or PMA and observed adhesion to fibronectin (FN). As expected, 80 to 90% of PMA-activated MCP5/L cells or BMCMC adhered to FN. In addition, SCF promoted MCP5/L cell or BMCMC adhesion to FN in a dose-response fashion with 50 to 60% of BMCMC adhering to FN at a concentration 10 ng/ml of SCF. BMCMC adhesion was observed with as little as 200 pg/ml of SCF. Adhesion of SCF stimulated BMCMC to FN did not require IL-3, but was dependent on the concentration of FN used to coat the assay surface. Mast cell adhesion in the presence of SCF appeared to occur through an integrin receptor as adhesion was calcium dependent and could be blocked by an RGD (Ang, Gly, Asp)-containing peptide. SCF did not directly mediate adhesion through interaction with c-kit, as FN-coated surfaces exposed to SCF before initiation of the adhesion assay did not promote adhesion in the absence of soluble SCF. Rather, SCF appeared to stimulate adhesion to FN by activating mast cells through its interaction with c-kit. Thus, antibody to SCF blocked adhesion, and rat and murine SCF stimulated BMCMC adhesion to FN, but human SCF, which does not bind to murine c-kit, did not stimulate adhesion. Genistein, which inhibits tyrosine kinase activity, partially inhibited SCF-induced adhesion. SCF thus stimulates mast cell adhesion and, because SCF is produced normally in tissues, it may be a major factor responsible for the adhesion of mast cells to connective tissue matrix under physiologic conditions.
Tyrosine phosphorylation provides an obligatory early signal for Fc gamma RII-mediated endocytosis in the monocytic cell line THP-1.
Authors: Ghazizadeh S , Fleit H B 
Published: December 2022

Abstract
The human monocytic cell line THP-1 expresses two classes of IgG Fc receptor (Fc gamma R), Fc gamma RI, a high affinity 72-kDa Fc gamma R, and Fc gamma RII, a low affinity 40-kDa Fc gamma R. Biochemical as well as indirect immunofluorescence studies demonstrated that the selective cross-linking of Fc gamma RII with either anti-Fc gamma RII mAb Fab followed by F(ab)2 fragments of goat anti-mouse IgG, or aggregated hIgG1, which represents a physiologic ligand for this receptor, resulted in the activation of a protein tyrosine kinase (PTK). Several distinct cellular proteins including the Fc gamma RII itself were specifically phosphorylated on tyrosine upon ligand binding. Cross-linking of Fc gamma RII also triggered a rapid internalization of Fc gamma RII that was dependent upon tyrosine kinase activity. The internalization of the receptor in endocytic vesicles was established by confocal microscopy. The time course of Fc gamma RII-initiated tyrosine phosphorylation paralleled endocytic events and reached a maximum between 5 and 10 min after ligand binding and declined toward basal levels as endocytosis was completed. Identical concentrations of genistein, an inhibitor of PTK, blocked Fc gamma RII-mediated endocytosis as well as the induction of tyrosine phosphorylation of Fc gamma RII and other cellular proteins. Cross-linking of Fc gamma RI also induced a rapid tyrosine phosphorylation of cellular proteins similar to the Fc gamma RII-mediated events. However, Fc gamma RII was not tyrosyl phosphorylated upon Fc gamma RI activation. Thus Fc gamma RII is a unique substrate for the PTK activity associated with Fc gamma RII upon cross-linking of this receptor. These results support the conclusion that Fc gamma RII is capable of independent signaling on monocytic cells and that protein tyrosine phosphorylation is an obligatory proximal signal for Fc gamma RII-mediated endocytosis. Furthermore, the signaling pathways employed by Fc gamma RI and Fc gamma RII are likely to be distinct.
Circulating T cell repertoire complexity in normal individuals and bone marrow recipients analyzed by CDR3 size spectratyping. Correlation with immune status.
Authors: Gorski J , Yassai M , Zhu X , Kissela B , Kissella B [corrected to Kissela B ] , Keever C , Flomenberg N 
Published: December 2022

Abstract
The analysis of the T cell repertoires involved in local or systemic immune responses is beginning to play an important role in many clinical situations. These include autoimmunity, response to viral or bacterial superantigens, alloimmunity including allograft rejection, and tumor immunity. Here we analyze circulating T cell repertoires by determining TCR beta-chain gene complexity using a modification of V beta family-specific PCR. This approach, called CDR3 size spectratyping, uses the size heterogeneity of the CDR3 as a further source of specificity in TCR analysis. It has been used here to analyze the complexity and stability of circulating T cell repertoires in normal adults, including bone marrow donors, and bone marrow transplant recipients. Normal spectratypes are both complex and stable. The repertoire complexity of marrow recipients correlates with their state of immune function. Contractions and gaps in repertoires are revealed in individuals suffering from recurrent infections associated with T cell impairment. Spectratype analysis is applicable to other studies of specific repertoire skewing such as may be associated with immunodeficiency or found at sites of immune activity.
Costimulation through CD28 enhances T cell-dependent B cell activation via CD40-CD40L interaction.
Authors: Klaus S J , Pinchuk L M , Ochs H D , Law C L , Fanslow W C , Armitage R J , Clark E A 
Published: December 2022

Abstract
Changes in T cell helper function were analyzed when anti-CD3-activated T cells were costimulated with mAbs to the CD28 receptor (anti-CD28). T cell-dependent B cell growth and differentiation were consistently augmented if anti-CD3 stimulated-T cells were simultaneously activated with anti-CD28. Although anti-CD28 enhanced IL-2 and IL-4 production, it did not increase B cell responses solely by augmenting production of soluble lymphokines. Anti-CD28 costimulation induced increases on T cells of CD40 ligand (CD40L), known to promote B cell proliferation and Ig secretion. Because anti-CD28 promoted T cell helper functions and expression of CD40L, we examined the dependence for CD40L during T cell-dependent B cell responses. Although soluble CD40 fusion proteins only partially inhibited T cell-dependent B cell activation, we found a strict requirement for CD40L expression at initiating B cell responses. Both CD40L expression and T cell help were blocked by cyclosporin A after TCR cross-linking, and, unlike T cell proliferation, both remained cyclosporin A sensitive during CD28 costimulation. In addition, anti-CD28 could not compensate for the T cell helper deficiency of hyper IgM syndrome patients who lack functional CD40L. Thus, anti-CD28-induced T cell help is delivered via a CD40L-dependent process. The fact that cross-linking CD40 on B cells promotes expression of the B7/BB-1 ligand for CD28 suggest T and B interactions may have a reciprocal amplification mechanism.