bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lymphokine mRNA expression by transplantable murine B lymphocytic malignancies. Tumor-derived IL-10 as a possible mechanism for modulating the anti-tumor response.
Authors: Bost K L , Bieligk S C , Jaffe B M 
Published: December 2022

Abstract
In vitro and in vivo expressions of cytokine mRNAs by four transplantable murine B lymphocytic malignancies designated A20, MOPC 315, 2PK-3, and RAW 8.1 were determined using sensitive reverse-transcribed (RT)-PCR. Despite significant differences in both the stage of B cell differentiation represented by each cell line and the method used to induce the original B lymphocytic tumors, IL-6 and IL-10 mRNAs were detected in each of the cultured cell lines. Whereas IL-2, IL-4, IL-5, and IL-12 mRNAs were not detected in cultured cells, expression of cytokine mRNAs in solid tumor tissue was quite different. RT-PCR of poly(A)+ RNA isolated from each of the four solid tumors demonstrated the presence of IL-4, IL-5, IL-6, IL-10, TGF-beta 1, and TNF-alpha mRNAs. There was a noticeable lack of significant IL-2 mRNA expression in any of the solid tumors. Using RT-PCR, it was clear that each of the malignant B lymphocytes expressed IL-6, IL-10, TGF-beta 1, and TNF-alpha, with limited expression of IL-4 and IL-5. To explore the mechanisms that might contribute to the lack of IL-2 mRNA in these solid tumors, quantitative competitive (QC)-RT-PCR was used to quantify expression of IL-10 mRNA. MOPC 315 tumor expressed the most IL-10 mRNA (23.2 pg/micrograms of poly(A)+ RNA), whereas 2PK-3, A20, and RAW 8.1 tumors expressed 7.4, 2.6, and 0.6 pg/micrograms of poly(A)+ RNA, respectively. Secretion of IL-10 into culture supernatants or into sera and ascitic fluid of tumor-bearing animals correlated with mRNA expression. This dysregulated IL-10 production in animals with B lymphocytic tumors suggested a mechanism that may account for the lack of IL-2 mRNA expression in solid tumors, and suggested a possible mechanism by which malignant B lymphocytes may limit cell-mediated antitumor responses.
Reactivity of autologous CD4+ T lymphocytes against human melanoma. Evidence for a shared melanoma antigen presented by HLA-DR15.
Authors: Takahashi T , Chapman P B , Yang S Y , Hara I , Vijayasaradhi S , Houghton A N 
Published: December 2022

Abstract
Reactivity of CD8+ T lymphocytes against human melanoma has been extensively characterized, but little is known about melanoma Ags recognized by CD4+ lymphocytes. We have identified CD4+ CTL that recognize shared melanoma Ag(s) expressed by autologous melanoma cells and a subset of allogeneic melanomas. The same Ag(s) was shared by autologous and positive allogeneic melanomas by cross-blocking experiments. Cytotoxicity was directed against epitopes presented by HLA-DR on target melanoma cells, and allelic typing revealed that cytotoxicity was restricted through HLA-DR15. These CD4+ T cells released IFN-gamma, IL-4, and TNF-alpha, but not IL-2, in response to HLA-DR15+ target cells. CD4+ T cells did not lyse DR15+ nonmelanoma cell types, including melanocytes or fibroblasts (induced to express HLA-DR by IFN-gamma). Thus, by cytotoxicity assays, shared Ags were only recognized on melanoma cells but not on normal melanocytes. In summary, this analysis shows that melanoma cells share an Ag that is presented by HLA-DR15.
Induction of human serum amyloid A in Hep 3B cells by IL-6 and IL-1 beta involves both transcriptional and post-transcriptional mechanisms.
Authors: Jiang S L , Lozanski G , Samols D , Kushner I 
Published: December 2022

Abstract
Previous studies of murine serum amyloid A (SAA) regulation during inflammatory states or following exposure to macrophage-conditioned medium have raised the possibility that both post-transcriptional and transcriptional mechanisms participate in induction of this family of proteins. Since IL-6 and IL-1 have been shown to induce SAA in human hepatoma cell lines, we explored the possibility that these cytokines might induce human SAA through post-transcriptional as well as transcriptional mechanisms. In kinetic studies, we found that continuous exposure of Hep 3B cells to either IL-6 or IL-1 beta alone caused only minimal increases in SAA mRNA and marginal increases in transcription (as measured by nuclear runon). In contrast, the combination of these cytokines led to a 23-fold increase in transcription, maximal at 12 h, with continuing increase in mRNA, achieving levels more than 1,000-fold greater than baseline by 72 h. This massive disparity between increases in mRNA and in transcription rate strongly supports the participation of post-transcriptional mechanisms in SAA induction by (IL-6 + IL-1 beta), whereas the lag between peaks of transcription and mRNA abundance reflects a relatively slow degradation rate of SAA mRNA. As observed by other workers, mean size of SAA mRNA decreased progressively over the course of incubation. Simultaneous kinetic studies of complement factors B and C3, haptoglobin, and alpha-1 protease inhibitor revealed several different patterns of response to IL-6 and IL-1 beta.
Activation of human monocytes by streptococcal rhamnose glucose polymers is mediated by CD14 antigen, and mannan binding protein inhibits TNF-alpha release.
Authors: Soell M , Lett E , Holveck F , Schöller M , Wachsmann D , Klein J P 
Published: December 2022

Abstract
The present work was initiated to define mechanisms that account for the binding on human monocytes of streptococcal cell wall polysaccharides formed by rhamnose glucose polymers (RGPs), and subsequent stimulatory activities. We show here that RGPs bind to and stimulate human monocytes to produce TNF-alpha in a dose-dependent manner. To detect cell surface RGPs binding proteins, intact monocytes were biotinylated before lysis with Nonidet P-40 and solubilized proteins were incubated with RGPs Affi-Prep beads. One major membrane protein of 55 kDa was specifically detected and identified as CD14 because it reacted with anti-CD14 mAbs. Furthermore, anti-CD14 mAbs were able to perform a dose-dependent inhibition of RGPs binding, and suppressed TNF-alpha release from RGPs-stimulated monocytes. Moreover, we demonstrated that RGPs also bind to CD11b; however, this binding is not implicated in synthesis of TNF-alpha. Interestingly, RGPs binding to monocytes was enhanced by human normal serum (HNS) whereas HNS inhibits the TNF-alpha-stimulating activity of RGPs. Western blotting analysis of HNS proteins purified on RGPs Affi-prep beads revealed three specific bands of 75, 55, and 32 kDa reactive with anti-C3 Abs, anti-CD14 mAbs (TUK4), and anti-human mannan binding protein (hMBP)-derived peptide IgG, respectively. These results suggest that C3, soluble CD14, and hMBP form complexes that are probably active in enhancing the binding of RGPs to monocytes. Additional studies have shown that hMBP that recognizes RGPs prevents, unlike the LPS binding protein, TNF-alpha release by inhibiting the binding of RGPs to CD14 Ag. By incubating cells with a constant amount of RGPs-hMBP complexes in the presence or absence of increasing concentrations of C1q, we also demonstrated that C1q receptor mediates the binding and probably the uptake of RGPs-hMBP complexes by human monocytes.
Perturbed development of T and B cells in mice expressing an Hlx homeobox transgene.
Authors: Allen J D , Harris A W , Bath M L , Strasser A , Scollay R , Adams J M 
Published: December 2022

Abstract
Within the lymphoid compartment of mice, the Hlx homeobox gene is expressed only at early stages of B-lymphoid differentiation. To determine whether Hlx influences lymphopoiesis, transgenic mice were developed to enforce Hlx expression throughout the B and T cell lineages. The strain with the highest transgene expression in both cell types (Hlx-94) exhibited marked perturbations in both B and T cell development. In these mice, the thymus lacked almost all mature CD4+8- and CD8+4- cells and the medulla was greatly shrunken, whereas nearly one-half the T cells in the periphery were CD4+8+, a cell type normally confined to the thymus. The peripheral CD4+8+ cells had some features of mature T cells, including responsiveness to mitogens. Presumably these cells had emigrated prematurely from the thymus and generated mature T cells in the periphery. Bone marrow transplantation experiments indicated that the defects was intrinsic to the Hlx-94 hematopoietic cells rather than support cells. Although thymocyte development in Hlx-94 mice was blocked at the stage when selection normally occurs, analysis of lymphocyte populations in the progeny of crosses with mice transgenic for an anti-HY T cell receptor indicated that neither positive nor negative selection of T cells was markedly affected. In addition to T cell defects, Hlx-94 mice had subnormal numbers of B lymphoid cells in the bone marrow and spleen, and their surface phenotype suggested that B cell development after the pro-B stage was impeded. Furthermore, the B cell response to stimulation with LPS was impaired. These striking developmental defects suggest that the Hlx gene may help to govern lymphoid maturation.
Role of IL-12 in human B lymphocyte proliferation and differentiation.
Authors: Jelinek D F , Braaten J K 
Published: December 2022

Abstract
The role of IL-12 in human peripheral blood B cell responsiveness was examined. To analyze the ability of IL-12 to directly mediate B cell growth and/or differentiation, FACS-purified (&gt; 99% pure) B cells were studied and a polyclonal B cell-activating system utilizing Cowan I Staphylococcus aureus was used. Whereas IL-2 is highly effective in this system in promoting both B cell growth and differentiation, IL-12 was observed only to augment modestly B cell growth and to be ineffective by itself as a B cell differentiation factor for S. aureus-stimulated B cells. However, IL-12 markedly enhanced Ig secretion when added in the presence of IL-2. Moreover, when the ability of IL-12 to augment IL-2-dependent B cell Ig secretion was compared with the ability of several known auxiliary B cell differentiation factors, IL-12 was observed to be the most potent cytokine that could costimulate with IL-2. Analysis of IL-12-stimulated B cell cultures failed to reveal outgrowth of T cells and NK cells. In addition, assessment of IFN-gamma levels in IL-12-driven B cell culture supernatants and analysis of IFN-gamma effects on B cell responses added additional support to the conclusion that IL-12 directly modulates B cell function. Finally, these results suggest that IL-12 is a potent constimulus of B cell differentiation and that the signals conveyed by IL-12 seem to be qualitatively distinct from the differentiative signals delivered by other cytokines such as IL-2.
TGF-beta 1 and cyclic AMP promote apoptosis in resting human B lymphocytes.
Authors: Lømo J , Blomhoff H K , Beiske K , Stokke T , Smeland E B 
Published: December 2022

Abstract
TGF-beta and agents that elevate intracellular cAMP levels are potent inhibitors of B cell activation in vitro and have been shown to arrest stimulated B cells in the G1 phase of the cell cycle. We tested the effects of TGF-beta 1 and the cAMP-inducing agent, forskolin, on the viability of resting B cells from human peripheral blood, and found that both agents caused a significant, dose-dependent increase in cell death relative to spontaneous death in medium alone, as measured by vital dye staining with propidium iodide. Apoptosis was shown to be the overall mode of death by demonstrating DNA fragmentation using DNA nick end labeling and by verifying the characteristic morphologic changes. In contrast with TGF-beta 1 and forskolin, various B cell activation stimuli generally inhibited spontaneous apoptosis of resting cells. The most potent effects were observed with IL-4 and the phorbol ester, O-tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C. IL-4 also partly inhibited TGF-beta 1 and forskolin-induced apoptosis. In contrast, TPA completely reversed cell death in forskolin-treated cultures, but had no effect on TGF-beta 1-induced apoptosis, indicating that TGF-beta 1 and forskolin promote apoptosis by different mechanisms. The relative protein expression of bcl-2, a proto-oncogene that inhibits apoptosis, was unaltered by the apoptotic as well as the survival stimuli tested, suggesting that apoptosis was regulated by a bcl-2-independent mechanism. We conclude that apoptosis is a regulated phenomenon in resting human B cells. Furthermore, TGF-beta and cAMP may inhibit B cell responses not only by blocking cell cycle progression in activated cells, but also by inducing apoptosis in resting cells.
Transplantable NK cell progenitors in murine bone marrow.
Authors: Moore T , Bennett M , Kumar V 
Published: December 2022

Abstract
Differentiation of NK cells from pluripotent hematopoietic stem cells is a poorly understood process. Although it is known that NK cells are bone marrow derived and dependent upon an intact bone marrow microenvironment for complete maturation, it is not known if they arise from an intermediate lymphoid stem cell or from progenitors exclusively committed to the NK lineage. To determine whether phenotypically distinct committed NK progenitor cells exist in murine bone marrow, we sorted cells capable of repopulating recipient mice with mature NK cells upon i.v. transfer. We identified a rare population of bone marrow cells with the phenotype Ly6+ Lin- c-kit+ CD43high Fall-3high TSA-1- AA4.1low Rh123high that is highly enriched for the ability to generate NK cells after transplantation. Although these cells are relatively depleted of Rh123low pluripotent stem cells, they are highly enriched for both lymphoid and myeloid repopulating ability. Thus, we have found no evidence to support the existence of a phenotypically distinct transplantable progenitor population in mouse bone marrow that is either exclusively committed to the NK cell lineage or exhibits the functional characteristics of a common lymphoid stem cell.
Induction of long-lasting immunity to Plasmodium yoelii malaria with whole blood-stage antigens and copolymer adjuvants.
Authors: Hunter R L , Kidd M R , Olsen M R , Patterson P S , Lal A A 
Published: December 2022

Abstract
We previously reported that protection of mice from nonlethal Plasmodium yoelii malaria by immunization with whole killed blood-stage parasites was dependent on the adjuvant and that adjuvants influenced both the specificity and isotype of Ab. Additional studies with the most effective formulations were undertaken to better define the protective responses and 100% protection from lethal P. yoelii malaria was produced by three immunizations with Ag in copolymer P1004 and detoxified RaLPS as adjuvants and 83% protection was induced by a single immunization. The protection lasted for 9 mo and was associated with an anamnestic rise in Ab titer of the IgG2a isotype during the challenge infection. Passive immunization with Ab from animals that had been immunized and challenged transferred sterile immunity. Splenectomy reduced, but did not abolish, protection. These data suggest that the effective Ab is directed against labile epitopes on the surface of blood-stage parasites. The vaccines primed animals for production of such Ab, but its synthesis was efficiently induced only by challenge with live organisms.
Limited T cell antigen receptor repertoire in tumor-infiltrating lymphocyte and inhibition of experimental lung metastasis of murine melanoma by anti-TCR antibody.
Authors: Wang R , Taniguchi M 
Published: December 2022

Abstract
We analyzed the variability of T cell Ag receptor in tumor-infiltrating lymphocytes in primary and metastatic melanomas. Using a very sensitive inverse/double step PCR, we found the preferential V alpha usage of TCR in tumor-infiltrating lymphocytes in which some TCR sequences were homogenous. However, the profile of TCR V alpha expression was different in primary and metastatic melanomas. V alpha 8+, V alpha 2+, V alpha 4+, and V alpha 3+ TCR were the most dominant repertoires in primary melanoma, whereas V alpha 3+ and V alpha 4+ TCR dominated metastatic melanoma. Depletion of V alpha 3 T cells by the injection of tumor-bearing mice with anti-V alpha 3 Ab resulted in protection against experimental lung metastasis, indicating that V alpha 3+ regulatory T cells exist in the tumor site and help metastatic tumor growth.
Isotype switching from IgG3 to IgG1 converts a nonprotective murine antibody to Cryptococcus neoformans into a protective antibody.
Authors: Yuan R , Casadevall A , Spira G , Scharff M D 
Published: December 2022

Abstract
Passively administered mAbs to Cryptococcus neoformans capsular polysaccharide can alter the course of infection in mouse models. In preliminary studies of passive Ab efficacy, most IgM, IgA, and IgG1 mAbs were protective, but the few IgG3 mAbs tested did not confer significant protection. Because IgG3 is effective in pneumococcal infections, this phenomenon was examined more rigorously by generating an IgG1 switch variant from the non-protective IgG3 mAb 3E5 and comparing its protective efficacy in a murine model of i.v. infection by using strains of both the A and D serotypes. The 3E5 IgG3 mAb did not prolong survival or reduce organ fungal burden. Rather, the IgG3 decreased survival relative to controls. In contrast, the IgG1 switch variant of 3E5 significantly prolonged survival, reduced organ colony-forming units, and reduced serum polysaccharide Ag level in infected mice. The results establish that isotype is important for Ab efficacy against C. neoformans.
IL-4 renders mast cells functionally responsive to endothelin-1.
Authors: Egger D , Geuenich S , Denzlinger C , Schmitt E , Mailhammer R , Ehrenreich H , Dörmer P , Hültner L 
Published: December 2022

Abstract
It has previously been shown that mouse bone marrow-derived mast cells (BMMC) synthesize and secrete endothelin-1 (ET-1) and express ETA-type endothelin receptors (ETA-R). The study presented here was designed to elucidate the influence of different cytokine conditions for cellular differentiation and maturation on the ability of primary mouse BMMC to respond to exogenous ET-1. BMMC were grown for 2 wk in IL-3 alone and then cultured for 2 to 3 wk with kit ligand (KL) and/or IL-3 in the presence or absence of IL-4. ET-1 induced a very rapid (&lt; or = 1 min) and dose-dependent release of histamine and serotonin from BMMC cultured in the presence of both IL-3 and IL-4. The effect of ET-1 was quantitatively comparable with IgE/Ag-induced mediator release and comprised up to 20% and 16% of total cellular histamine and serotonin, respectively. In BMMC grown with KL or KL plus IL-3, a substantial effect of ET-1 on amine release was only observed when IL-4 had been included in the culture medium. These IL-4 effects could not be observed if BMMC grown in IL-3 and/or KL were preincubated for 1 or 24 h with IL-4 before activation with ET-1, suggesting that a differentiation process rather than a functional priming effect had been initiated by IL-4. In BMMC, the histamine and serotonin release induced by ET-1 (10(-6) M) was inhibited by an ETA-R-specific antagonist (cyclic [D-Asp-Pro-D-Val-Leu-D-Trp]) in a dose-dependent manner, with complete inhibition at an antagonist concentration of 10(-8) M. ET-1 stimulated leukotriene C4 biosynthesis up to 4.5-fold in BMMC cultured in the presence of IL-4. No such ET-1 effect was observed in BMMC cultured in media containing IL-3, KL, or a combination of both cytokines. Peritoneal cells (containing 2 to 3% serosal mast cells) obtained from BALB/c mice released 87 +/- 2% of histamine within 1 min after challenge with ET-1. Our results demonstrate that ET-1 can directly act as a histamine and serotonin secretagogue and as a stimulator of leukotriene C4 production in mast cells. IL-4 appears to be critically involved in the differentiation of immature mast cell precursors to an ET-1-reactive phenotype.(ABSTRACT TRUNCATED AT 400 WORDS)
Compartmentalized expression of RANTES in a murine model of endotoxemia.
Authors: VanOtteren G M , Strieter R M , Kunkel S L , Paine R , Greenberger M J , Danforth J M , Burdick M D , Standiford T J 
Published: December 2022

Abstract
Systemic exposure to LPS initiates a complex sequence of events culminating in organ-specific leukocyte recruitment and end organ injury. We hypothesized that RANTES, a C-C chemokine with potent M phi (mononuclear phagocyte) chemotactic activity, is expressed in vivo in response to endotoxemia, and that this protein may play an important role in the recruitment of M phi to the lung. CD-1 mice were challenged with LPS (200 micrograms), resulting in a maximal fourfold increase in polymorphonuclear leukocyte (neutrophils) at 6 h post LPS, and a 2.4-fold increase in numbers of M phi within lung minces at 24 h. A time-dependent increase in RANTES mRNA was detected in lung after LPS treatment, whereas minimal quantities of RANTES mRNA were detected in blood buffy coats and liver. Furthermore, treatment with LPS resulted in time-dependent increase in RANTES protein within lung homogenates, with immunolocalization to alveolar epithelial cells. The pretreatment of mice with goat anti-RANTES Ab significantly inhibited the influx of lung M phi, but not polymorphonuclear leukocyte and lymphocytes, at 24 h post-LPS challenge. Lastly, the pretreatment of animals with soluble TNF receptor: Ig construct 2 h before LPS resulted in a 60% reduction in steady state levels of RANTES mRNA within lung homogenates at 4 h post-LPS. Our observations suggest that RANTES represents an important mediator of lung M phi recruitment in the setting of endotoxemia, and that the expression of RANTES in vivo is dependent upon the endogenous production of TNF.
Circulating forms of ICAM-3 (cICAM-3). Elevated levels in autoimmune diseases and lack of association with cICAM-1.
Authors: Martin S , Rieckmann P , Melchers I , Wagner R , Bertrams J , Voskuyl A E , Roep B O , Zielasek J , Heidenthal E , Weichselbraun I 
Published: December 2022

Abstract
The intercellular adhesion molecule-3 (ICAM-3) has been identified as the third LFA-1 ligand in addition to ICAM-1 and ICAM-2. In this report we have identified circulating forms of ICAM-3 (cICAM-3) in human serum. Using a sandwich ELISA with two monoclonal anti-ICAM-3 Abs, we detected cICAM-3 in concentrations between 40 and 360 ng/ml in all of 112 healthy controls. An analysis of patient sera from 10 different immune-mediated diseases revealed a distinct pattern of expression. Significantly elevated cICAM-3 levels were found in rheumatoid arthritis, systemic lupus erythematosus, Guillain-Barré syndrome, and multiple sclerosis, but not in type I diabetes, Grave's disease, chronic autoimmune thyroiditis, ulcerative colitis, or Crohn's disease. cICAM-3 levels were significantly higher in systemic lupus erythematosus patients with active compared with nonactive disease. Despite their binding to the same integrin receptor, serum levels of cICAM-3 did not correlate with cICAM-1 concentrations in either normal persons or in patients. The majority of patients had either elevated cICAM-3 or cICAM-1 levels but not both. In conclusion, a circulating form of ICAM-3 is present in human sera. cICAM-3 expression is elevated in certain immune-mediated diseases but occurs independently of cICAM-1.