bluuebunny/crossref_metadata_2025_split huggingface dataset:
p55 IL-2 receptor mRNA precursors in murine T lymphocyte nuclei.
Authors: Froussard P , Chastagner P , Sommé G , Abadie A , Greene W , Thèze J , Longacre S 
Published: December 2022

Abstract
An unusual family of cDNA clones homologous to human p55 IL-2R sequences was isolated from the murine HT-2 Th cell line. These clones were mapped, partially sequenced, and compared with previously published human and mouse IL-2R sequences. They appear to consist of various combinations of exons and introns, suggesting that they are derived from p55 IL-2R mRNA precursors. The configuration of exons in the splicing intermediates indicates that the murine and human gene organizations are similar and that the 3' end of intron 3 is well conserved between the two species. RNA mapping experiments using nuclear, cytoplasmic, and total RNA and probes derived from various parts of the p55 IL-2R gene support and extend the sequence data. They indicate that detectable amounts of immature p55 IL-2R mRNA are found specifically in the cell nucleus of the HT-2 cell line. Similar data were obtained for the Th cell clone 52.3 and the cytotoxic T cell line CTLL. All these results indicate that the T cell nucleus contains significant amounts of immature p55 IL-2R mRNA.
Human beta 2-microglobulin specifically enhances cell-surface expression of HLA class I molecules in transfected murine cells.
Authors: Perarnau B M , Gillet A C , Hakem R , Barad M , Lemonnier F A 
Published: December 2022

Abstract
Sequential transfections of P815 murine mastocytoma cells with class I gene encoding either HLA-Cw3, HLA-A3, or HLA-B7 H chain and subsequently with a human beta 2-microglobulin gene were performed to evaluate the relative efficiency of human and murine beta 2-microglobulins in promoting the cell-surface expression of HLA-class I molecules. A 6-, 11-, and 40-fold specific enhancement of the cell-surface expression of HLA-Cw3, HLA-A3, and HLA-B7 molecules, respectively, was observed in cells co-transfected with human beta 2-microglobulin gene. This effect was attributed to a more efficient association of HLA H chains with human than with murine beta 2-microglobulin, which apparently allowed a more rapid transport of the HLA molecules from the endoplasmic reticulum to the Golgi apparatus.
Synergistic in vitro and in vivo anti-tumor effect of daunomycin-anti-96-kDa melanoma-associated antigen monoclonal antibody CL 207 conjugate and recombinant IFN-gamma.
Authors: Matsui M , Nakanishi T , Noguchi T , Ferrone S 
Published: December 2022

Abstract
The mAb CL 207 recognizes a 96-kDa melanoma-associated Ag. The latter is not modulated by antibody but is highly susceptible to induction by immune IFN-gamma on human carcinoma and melanoma cells. The mAb CL 207 does not mediate C- and cell-dependent lysis of human carcinoma and melanoma cells. Conjugation of daunomycin with mAb CL 207 causes a slight reduction of its immunoreactivity and affinity but does not affect its serologic specificity or the toxicity of daunomycin. In combination with IFN-gamma, the daunomycin-mAb CL 207 conjugate displays a selective in vitro and in vivo toxic effect on tumor cells that express the 96-kDa MAA. The synergistic effect of IFN-gamma and daunomycin-mAb CL 207 conjugate is specific. The in vivo toxicity is influenced by the interval between injection of human tumor cells into nude mice and that of IFN-gamma and daunomycin-mAb CL 207 conjugate. The present results suggest that the 96-kDa melanoma-associated Ag may be a useful model to investigate the combined use of IFN-gamma and mAb for the selective destruction of tumor cells.
The expression and regulation of a potential lymphokine gene (TCA3) in CD4 and CD8 T cell clones.
Authors: Wilson S D , Burd P R , Billings P R , Martin C A , Dorf M E 
Published: December 2022

Abstract
The TCA3 gene was originally isolated from a cDNA library derived from a TH1 (inflammatory) T cell clone. Expression of TCA3 RNA was limited to cells in the activated state. Based on its expression profile and the existence of a hydrophobic leader sequence with a predicted cleavage site, we proposed that TCA3 encodes a new lymphokine. In the present study, we examine the subset distribution, kinetics, and regulation of TCA3 RNA expression. We show that TCA3 is expressed in response to selected T cell-activating stimuli. TCA3 is transcribed to peak steady state levels by 4 h after stimulation in TH1, TH2 (helper), and CTL clones. Two intracellular signals, supplied in vitro by phorbol ester and one of several agents capable of increasing intracellular free calcium concentrations, are required for the initiation of TCA3 transcription. In addition, TCA3 transcription is blocked by anti-L3T4 mAb, suggesting that prior signaling through L3T4 can inhibit expression of TCA3 and other lymphokines. In contrast to IL-2, IL-4, and IFN-gamma TCA3 is uniformly expressed at high levels among all individual T cell clones examined, including four TH1, three TH2, and three CTL clones. Furthermore, activation-specific TCA3 expression can be dissociated from T cell proliferation.
Induction of macrophage Ia antigen expression by rIFN-gamma and down-regulation by IFN-alpha/beta and dexamethasone are regulated transcriptionally.
Authors: Fertsch-Ruggio D , Schoenberg D R , Vogel S N 
Published: December 2022

Abstract
In previous studies, the induction of Ia Ag on murine macrophages by rIFN-gamma and the antagonism of this induction by IFN-alpha/beta and glucocorticoids were examined. These findings showed that both the induction of Ia Ag by rIFN-gamma, as well as the antagonism of rIFN-gamma-induced Ia Ag expression by IFN-alpha/beta and dexamethasone, are regulated by cognate changes in Ia mRNA. In the present report, this observation was first extended to show that the decreased steady-state level of Ia-specific mRNA seen in the cytoplasm of macrophages treated with rIFN-gamma in the presence of IFN-alpha/beta or dexamethasone were also seen in nuclear RNA preparations. To test the hypothesis that alterations in the rate of Ia gene transcription were responsible for these changes in steady-state levels, nuclear "run on" transcription experiments were performed. The results indicate that both the induction of Ia gene expression by rIFN-gamma and its inhibition by IFN-alpha/beta or dexamethasone are regulated by changes in Ia gene transcription.
Monoclonal and anti-idiotypic anti-EBV/C3d receptor antibodies detect two binding sites, one for EBV and one for C3d on glycoprotein 140, the EBV/C3dR, expressed on human B lymphocytes.
Authors: Barel M , Fiandino A , Delcayre A X , Lyamani F , Frade R 
Published: December 2022

Abstract
Glycoprotein (gp) 140, the EBV/C3dR of B lymphocytes, is a membrane site involved in human cell regulation. To analyze the specificities of the binding sites for EBV and for C3d on the gp 140 molecule, two distinct approaches were used. First, anti-EBV/C3dR mAb were prepared against highly purified EBV/C3dR. Nine anti-EBV/C3dR mAb were obtained. Four of these anti-EBV/C3dR mAb inhibited C3d binding but not EBV binding on gp 140, whereas four others exerted an inverse effect. These differences could not be due to differences in isotype, antibody concentration, affinity constant, and number of molecules bound on cell surface, as these parameters were identical for the nine used mAb. Second, polyclonal anti-idiotypic antibodies (Ab2) were prepared against F(ab)'2 fragments of polyclonal anti-EBV/C3dR (Ab1). Ab2 recognized the variable portion of Ab1 as controlled by immunoblotting experiments. Ab2, which did not react with the cell surface, inhibited Ab1 binding on Raji cells. Ab2 mimicked the EBV/C3dR by its properties to bind to particle-bound C3d and EBV, preventing their binding on Raji cell surface. C3d binding specificities contained in Ab2 were isolated by affinity chromatography on C3b/C3bi-Sepharose. These specificities, being the internal image of C3d binding site of EBV/C3dR, reacted with Ab1 and inhibited particle-bound C3d binding on Raji cells but did not react with EBV. Taken together, these data support strongly that gp 140, the EBV/C3dR, carried two distinct binding sites, one for EBV and one for C3d.
Modulation of a human lymphoblastoid B cell line by cyclic AMP. Ig secretion and phosphatidylcholine metabolism.
Authors: Shearer W T , Patke C L , Gilliam E B , Rosenblatt H M , Barron K S , Orson F M 
Published: December 2022

Abstract
A transformed human B cell line, LA350, was found to be sensitive to cAMP-elevating agents by responding with rapid (0 to 2 h) severalfold elevations of intracellular cAMP to treatment with cholera toxin, isobutylmethylxanthine (IBMX), forskolin, and dibutyryl cAMP (all p less than 0.001). These cAMP-elevating agents also produced significant inhibitions of subsequent (48 to 72 h) Ig secretion by the same B cells as measured by a reverse hemolytic plaque assay and an enzyme-linked immunoadsorbent assay for IgM (both p less than 0.001). PMA- and IBMX-treated cells were particularly responsive to the effects of cholera toxin, showing a doubling of cAMP content and profound decrease in Ig production (p less than 0.001). Because our previous studies had correlated activation of the metabolic turnover of the phosphatidylcholine (PC) fraction of membrane phospholipids with enhanced Ig secretion, we examined the sensitivity of PC metabolism to cAMP in control and PMA-stimulated cells. Formation of PC was found to be inhibited by forskolin and IBMX (both p less than 0.002) but breakdown of PC was stimulated (p less than 0.001). These findings imply that as the enzymatic products of PC, choline phosphate and diacylglycerol, are depleted due to the combined effects of cAMP upon synthesis and turnover of PC, there is a decrease in Ig secretion. Since diacylglycerol activates protein kinase C, it appears reasonable that Ig secretion is at least partially regulated by cAMP-responsive alterations in PC metabolism produced by protein kinase C-induced phosphorylation. We conclude that the early cAMP-sensitive changes in PC metabolism in this activated B cell line may signal for subsequent alterations in Ig secretion.
Adoptive immunotherapy of microscopic and advanced visceral metastases with in vitro sensitized lymphoid cells from mice bearing progressive tumors.
Authors: Chou T , Bertera S , Chang A E , Shu S 
Published: December 2022

Abstract
Lymphocytes from mice bearing the weakly immunogenic MCA 105 sarcoma contained pre-effector cells that could be sensitized and expanded in vitro to acquire anti-tumor reactivity. The in vitro sensitization (IVS) required antigenic stimulation by tumor cells and the presence of IL-2 for cellular proliferation. Recent work has also demonstrated that IVS cells could be generated in an IL-2 concentration as low as 2 U/ml. In the present study, we have evaluated therapeutic efficacy of IVS cells generated in different concentrations of IL-2 against advanced metastases established in the lung as well as in the liver. Treatment of microscopic or grossly visible pulmonary metastases established for 3 or 10 days by systemic transfer of IVS cells resulted in significant reductions of the numbers of metastases. On a per cell basis, IVS cells generated in 2 U/ml of IL-2 exhibited at least twofold greater reactivity than cells generated in 1000 U/ml of IL-2. In survival experiments, treatment of established microscopic (day 3) and visible (day 10) pulmonary metastases with 1.5 x 10(7) and 3 x 10(7) IVS cells generated in 2 U/ml of IL-2 resulted in prolongation of survival and cure of the disease in 60 and 30% of animals, respectively. The systemic anti-tumor effect of IVS cells was further investigated in mice with hepatic metastases. Treatment of day 3 microscopic hepatic metastases revealed that as little as 1.2 X 10(7) IVS cells generated in 2 U/ml of IL-2 reduced the mean number of metastases from more than 250 in various control groups to 32. Evaluation by survival demonstrated that transfer of 1.7 x 10(7) and 3.8 x 10(7) IVS cells was capable of prolonging the survival and curing 40 and 30% of mice bearing day 3 and day 9 hepatic metastases, respectively. Again, IVS cells generated in 2 U/ml of IL-2 were more effective therapeutically than cells generated in 1000 U/ml of IL-2. In all experiments, mice were also given IL-2 to enhance the in vivo reactivity of IVS cells. However, the doses of IL-2 alone had no therapeutic benefit. Taken together, our results show that adoptive immunotherapy with IVS cells generated from tumor-bearing mice was an effective means of eliminating advanced metastases in various visceral organs.
Species-specific structural differences in the alpha 1 + alpha 2 domains determine the frequency of murine cytotoxic T cell precursors stimulated by human and murine class I molecules.
Authors: Engelhard V H , Le A X , Holterman M J 
Published: December 2022

Abstract
The frequency of murine CTL precursors (CTLp) that recognize the human histocompatibility Ag HLA-A2 and HLA-B7 was measured and found to be approximately two orders of magnitude lower than the frequency of CTLp that recognize murine H-2 alloantigens. The possible contribution of other cell surface molecules to this difference in response was addressed by expression of the H-2Ld molecule on a human cell and the HLA-B7 molecule on a murine cell. It was found that both human and murine H-2Ld expressing cells elicited comparable levels of H-2Ld specific CTL. Although murine HLA-B7 positive cells stimulated a higher frequency of HLA-B7-specific CTLp than did human cells, this appeared to be largely due to stimulation of CTLp that recognized HLA-B7 in the context of H-2 molecules; consequently, it was concluded that the difference in the frequency of murine CTLp elicited by human and murine class I Ag is due to species specific structural differences in these molecules. The regions of the class I molecule that were responsible for this difference were mapped using chimeric class I molecules constructed to replace domains of the human molecule with their murine counterparts. It was found that the frequency of CTLp is controlled by structures within the alpha 1 and alpha 2 domains of the molecule. These results are discussed in the light of models for T cell recognition of class I Ag and the diversification of the T cell receptor repertoire.
Mature T cells generated from single thymic clones are phenotypically and functionally heterogeneous.
Authors: Spangrude G J , Weissman I L 
Published: December 2022

Abstract
A limiting dilution system for cloning thymic CFU (CFUt) from murine bone marrow has been critically evaluated to test the clonal origin of the thymic colonies. Simultaneous limiting dilution transfer of three populations of bone marrow, each expressing a unique allelic cell surface determinant, resulted in independent segregation of donor-derived thymocyte populations within groups of recipient mice. Statistical analysis of the data allowed an estimate of 1 CFUt/3.3 x 10(4) i.v. transferred bone marrow cells. A pulse-chase experiment was utilized to establish whether CFUt seed directly to the thymus, or whether thymic seeding is secondary to extra-thymic engraftment. The results supported the conclusion that bone marrow CFUt utilize a specific interaction with thymic blood vessel endothelial cells to recognize and enter the thymus, and that this seeding occurs within 4 h of i.v. infusion. A kinetic analysis of emigration of the CFUt progeny into the peripheral blood revealed that, in most cases, an early wave of predominantly CD4+ CD8- lymphocytes emerges from the thymus approximately 4 wk after radiation and reconstitution. In a few cases, the first progeny of CFUt to emerge from the thymus were predominantly CD4- CD8+. Commitment of CFUt to TCR beta-chain rearrangements was assessed by quantitating expression of the V beta 8 family of TCR V region genes. Although some clones expressed a significantly higher or lower percentage of V beta 8+ cells, these differences were not stable with time. Thus, CFUt do not undergo absolute commitment to cell surface phenotype of TCR rearrangement, as reflected by the phenotypes of their progeny. Clones of mature peripheral progeny of CFUt could be expanded in culture in the presence of mitogen and growth factors; approximately 30 to 50% of proliferating clones could mediate cytotoxicity in a lectin-dependent assay, further indicating that CFUt are not absolutely committed to a particular T cell function.
IFN-gamma and prostaglandin E2 inhibit IL-4-induced expression of Fc epsilon R2/CD23 on B lymphocytes through different mechanisms without altering binding of IL-4 to its receptor.
Authors: Galizzi J P , Cabrillat H , Rousset F , Ménétrier C , de Vries J E , Banchereau J 
Published: December 2022

Abstract
Human rIL-4 specifically induces the expression of the low affinity receptor for IgE (Fc epsilon R2/CD23) on normal B cells and on the Burkitt lymphoma cell line Jijoye. IL-4 does not induce the generation of the second messenger cAMP in Jijoye cells. PGE2 (at 10(-7) M) was found to inhibit by 50% the IL-4 mediated Fc epsilon R2/CD23 induction on Jijoye cells. The PGE2 half maximum inhibitory concentration (1 nM) was comparable to that inducing a half maximal increase of intracellular cAMP (4nM PGE2). 8-bromo-cAMP (10(-3) M), forskolin (10(-5) M), and cholera toxin (100 ng/ml), which increase intracellular cAMP levels, also inhibited by 40 to 80% the IL-4 induced Fc epsilon R2/CD23 expression on Jijoye cells. PGE2 8-bromo-cAMP, forskolin, and cholera toxin also inhibited the IL-4-induced Fc epsilon R2/CD23 expression on normal B lymphocytes. Taken together these data suggest that PGE2 inhibits the IL-4 induced Fc epsilon R2/CD23 through an increase of intracellular cAMP. In contrast, IFN-gamma, which strongly inhibits IL-4-mediated Fc epsilon R2/CD23 expression on Jijoye cells, did not increase intracellular cAMP levels and thus probably acts through another mechanism. IFN-gamma and PGE2 did not inhibit binding of IL-4 to its receptor. It could be excluded that IFN-gamma and PGE2 were acting via an alteration/desensitization of the IL-4R inasmuch as 24 h pre-incubation of Jijoye cells with these agents affected neither the affinity of 125I-IL-4 for its receptor (Kd = 0.8 to 1.5 x 10(-10) M) nor the maximal number of binding sites per Jijoye cells (Bmax = 390 to 550). Furthermore, IFN-gamma and PGE2 did not affect the internalization and degradation of 125I-IL-4. These data demonstrate that PGE2 and IFN-gamma inhibit the IL-4-mediated induction of Fc epsilon R2/CD23 on B lymphocytes via different mechanisms that do not alter the interaction of IL-4 with its receptor.
Recombinant murine IL-5 induces high rate IgA synthesis in cycling IgA-positive Peyer's patch B cells.
Authors: Beagley K W , Eldridge J H , Kiyono H , Everson M P , Koopman W J , Honjo T , McGhee J R 
Published: December 2022

Abstract
Recent studies have shown that purified IL-5 from T cell lines and clones enhances IgA synthesis in LPS-triggered splenic B cell cultures, and that this effect is augmented by IL-4. In this study we have examined the ability of rIL-5 and rIL-4 to support spontaneous Ig synthesis in normal Peyer's patch (PP) B cell cultures. The rIL-4 supported proliferation of the HT-2 and in vivo adapted BCL-1 cell lines, increased Ia expression on normal spleen B cells, co-stimulated splenic B cell proliferation in the presence of anti-mu and enhanced IgG1 synthesis in LPS triggered splenic B cell cultures. The rIL-5 supported BCL-1 proliferation, co-stimulated splenic B cell proliferation in the presence of dextran sulfate, and increased IgA synthesis in LPS-stimulated splenic B cell cultures. Markedly enhanced IgA responses occurred in PP B cell, but not splenic B cell cultures supplemented with rIL-5 in the absence of an added B cell trigger. However, rIL-4 alone did not enhance IgA synthesis or increase the IgA synthesis of PP B cell cultures stimulated with rIL-5. The rIL-5 receptive PP B cells were present in the blast cell subpopulation, inasmuch as a low density fraction isolated on Percoll gradients accounted for the enhanced IgA synthesis. Further, cell cycle analysis of whole PP B cells using propidium iodide in conjunction with staining for surface B220, demonstrated that approximately 12 to 16% of the B cells were in the S and G2/M stages of cell cycle, the remainder being in Go + G1. The surface IgM+ B cells were predominantly in Go + G1, whereas the sIgA+ B cell subpopulation was enriched for cells in the S and G2/M compartments. The PP B cell subset responsible for enhanced IgA synthesis in the presence of rIL-5 was sIgA-positive because FACS-depletion of the sIgA+ B cells resulted in the total loss of rIL-5 enhanced IgA synthesis. Further, when PP B cells were enriched for sIgA+ B cells by cell sorting, these cells responded to rIL-5 with increased IgA synthesis in a dose-dependent manner. When the actual numbers of IgA secreting cells were assessed in PP B cell cultures with supplemental rIL-5, no significant increase in total IgA-producing cells was noted when compared with B cells cultured without rIL-5.(ABSTRACT TRUNCATED AT 400 WORDS)
The role of mast cells in thioglycollate-induced inflammation.
Authors: Qureshi R , Jakschik B A 
Published: December 2022

Abstract
The possible role of mast cells in the initiation of inflammation was studied in genetically mast cell-deficient mice, WBB6F1-W/Wv. Inflammation was induced by i.p. injection of thioglycollate. The influx of neutrophils was markedly delayed in WBB6F1-W/Wv mice as compared to the WBB6F1-+/+, mice (congeneic controls). At the time (14 h) of maximum influx of neutrophils in WBB6F1-+/+ mice, thioglycollate caused a 3-fold increase in the total cell number in the peritoneal lavage fluid, and the neutrophil count was elevated 14-fold. At the same time point in W/Wv mice, the total cell number in the peritoneal lavage fluid was not increased significantly and the neutrophils were increased only three- to four-fold. Not only was the neutrophil influx in WBB6F1-W/Wv mice delayed, but the length of time during which the neutrophil count was elevated in the peritoneal fluid was significantly shortened. Transfer (i.p.) of mast cells cultured from the bone marrow of congeneic controls corrected the delay in the neutrophil influx. The magnitude of the neutrophil influx in WBB6F1-W/Wv mice was equivalent to that of congeneic controls 9 days after mast cell repletion. Histologic studies were performed to follow the migration and differentiation of mast cells after adoptive transfer into WBB6F1-W/Wv mice. No connective tissue mast cells could be identified on day 9 when the inflammatory reaction was restored. Migration of mast cells into the tissue, as studied in the cecum, progressed steadily. On day 9 after adoptive transfer, the mast cell number was 38% of congeneic controls. Therefore, the increase in thioglycollate-induced neutrophil influx in WBB6F1W/Wv mice after mast cell repletion seemed to be correlated, at least to some extent, with the migration of mast cells into tissues and not with differentiation into connective tissue mast cells. However, a certain maturation and differentiation may have occurred. These results suggest that mast cells play an important role, although they do not seem to be the only cell type responsible for the initiation of inflammation.