bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL-1 serves as a secondary signal for IL-9 expression.
Authors: Schmitt E , Beuscher H U , Huels C , Monteyne P , van Brandwijk R , van Snick J , Ruede E 
Published: December 2022

Abstract
IL-9 is produced in vitro by activated CD4+ T cell lines of the Th2 subtype and by naive CD4+ T cells. Here we show that T cell lines stimulated with Con A in the presence of accessory cells (AC) such as irradiated spleen cells or bone marrow-derived macrophages produced substantially more IL-9 than T cells stimulated with Con A alone. These data suggest that AC influence the production of IL-9 through accessory signals that result in an at least 10-fold increase of IL-9 secretion by the respective T cells. Addition of IL-1 to T cells activated by Con A, PHA, or anti-CD3 antibodies revealed that this monokine was responsible for the potentiation of IL-9 production. This finding was confirmed by applying anti-IL-1 antibodies. The production of other lymphokines, namely, IL-3, IL-4, and IL-6, by activated T cells was not or only marginally enhanced in the presence of AC or IL-1, thus indicating that the synthesis of IL-9 is regulated differently from that of other Th2-derived lymphokines. Furthermore, it was demonstrated by Northern blot analysis that IL-1 increases IL-9 expression at the pretranslational level. Because IL-1 alone failed to induce the production of IL-9 by T cells, this monokine acts as a costimulator in combination with a T cell receptor-mediated signal.
IL-3 and IL-5 prime normal human eosinophils to produce leukotriene C4 in response to soluble agonists.
Authors: Takafuji S , Bischoff S C , De Weck A L , Dahinden C A 
Published: December 2022

Abstract
Eosinophils (Eos) produce large amounts of leukotriene C4 (LTC4) and platelet-activating factor (PAF) in response to calcium ionophore. However, the capacity of naturally occurring soluble agonists to promote lipid mediator formation by Eos is largely unknown. Our previous studies on neutrophils and basophils showed that certain hematopoietic growth factors are important regulators of lipid mediator formation. We examined LTC4 production by normal human Eos from healthy donors in response to soluble agonists with or without preincubation with the cytokines IL-3 and IL-5. Among three agonists (FMLP, C5a, PAF) tested over a wide concentration range, only FMLP induced some LTC4 formation by itself in normal Eos. However, after preincubation with IL-3 or IL-5, Eos produced detectable amounts of LTC4 in response to all three agonists. Eos primed by IL-3 or IL-5 generated at least 1 order of magnitude more LTC4 in response to FMLP as compared to C5a or PAF. FMLP-induced LTC4 production was enhanced by 26 to 635% (n = 16) and 67 to 611% (n = 12) after preincubation with IL-3 or IL-5, respectively. Priming for LTC4 production was concentration dependent occurring at IL-3 or IL-5 concentrations of 3 to 30 ng/ml and required an optimal preincubation period of 90 min. Thus, IL-3 and IL-5 profoundly modulate the production of lipid mediators by Eos in response to the soluble agonists FMLP, C5a, and PAF. Our data further support the importance of these cytokines in inflammatory reactions involving Eos.
Involvement of the CD11b/CD18 integrin, but not of the endothelial cell adhesion molecules ELAM-1 and ICAM-1 in tumor necrosis factor-alpha-induced neutrophil toxicity.
Authors: von Asmuth E J , van der Linden C J , Leeuwenberg J F , Buurman W A 
Published: December 2022

Abstract
TNF-alpha can incite neutrophil-mediated endothelial cell damage and neutrophil H2O2 release. Both effects require adherent neutrophils. Using specific mAb, we showed in this in vitro study that the CD18 beta 2-chain and the CD11b alpha M-chain of the CD11/CD18 integrin heterodimer have a major role in both TNF-alpha-induced neutrophil-mediated detachment of human umbilical vein endothelial cells and H2O2 release by TNF-alpha-activated human neutrophils. In contrast to anti-CD18 mAb, which consistently prevented neutrophil activation, anti-CD11a mAb and two of three anti-CD11b mAb did not reduce endothelial cell detachment and neutrophil H2O2 release, although they decreased neutrophil adhesion to human umbilical vein endothelial cells. mAb 904, directed against the bacterial LPS binding region of CD11b, reduced endothelial cell detachment for about 40% and neutrophil H2O2 release for more than 50%, demonstrating that CD11b/CD18 is engaged in TNF-induced neutrophil activation. Dependence on CD11b/CD18 could not be overcome by CD18-independent anchoring of neutrophils via PHA. Additionally, neither induction of increased expression of the endothelial cell adhesion molecules ICAM-1 and ELAM-1, nor subsequent addition of specific mAb, influenced endothelial cell injury or H2O2 release by TNF-activated neutrophils. Interaction with ICAM-1 and ELAM-1 therefore appears not to induce additional activation of TNF-stimulated neutrophils. These studies suggest that a specific, CD11b/CD18-mediated signal, instead of adherence only, triggers toxicity of TNF-activated neutrophils.
Complement activation induces the expression of decay-accelerating factor on human mesangial cells.
Authors: Shibata T , Cosio F G , Birmingham D J 
Published: December 2022

Abstract
In the present study we evaluated the effect of complement activation by immune complexes (IC) on the expression of decay-accelerating factor (DAF) on human mesangial cells (MC). MC in culture were incubated with an Ag (DNP-Gelatin) that binds to fibronectin present in the MC matrix. Subsequently, MC were incubated with anti-DNP antibodies in the presence of human serum. By immunoperoxidase staining we showed that these incubations resulted in IC formation and deposition of human C3 and terminal complement components (C5b-9) on the mesangial matrix and on the surface of MC. By immunoperoxidase staining and by RIA we showed that IC formation and complement activation significantly increased DAF expression on the MC plasma membrane. The induction of DAF expression was a consequence of deposition of terminal complement components on the MC because, zymosan-activated serum and IC formation in the presence of C5- or C8-deficient serum failed to increase MC DAF expression. Furthermore, the observed increased DAF expression was the consequence of increased DAF synthesis by MC. Thus, both cycloheximide and actinomycin D blocked the increase on MC DAF observed after incubation with IC and serum. MC DAF had biophysical and functional characteristics similar to DAF in other cells. Thus, 1) MC DAF was resistant to trypsin but was removed from the MC membrane by pronase; 2) phosphatidylinositol-specific phospholipase C removed 48 +/- 4% of MC DAF indicating that MC DAF is anchored in the cell membrane by phosphatidylinositol groups; 3) DAF isolated from MC-inhibited complement-mediated hemolysis and demonstrated a molecular mass of 83 kDa. In conclusion, deposition of terminal complement components on human MC trigger new synthesis and membrane expression of DAF. Because DAF protects cells against complement-mediated lysis, we postulate that DAF may protect glomerular cells during IC and complement-mediated glomerulonephritis.
Biochemical and functional analysis of extracellular stress proteins of Mesocestoides corti.
Authors: Estes D M , Teale J M 
Published: December 2022

Abstract
Previous studies of the serum antibody response in mice to Mesocestoides corti infection indicated that molecules released by the parasite influenced the production of IgM and IgG1 to the exclusion of other isotypes. Two proteins isolated from M. corti culture supernatants were found to be homologous to the 70-kDa heat shock proteins (hsp70) and Escherichia coli GroEL families of stress proteins. The proliferative responses of splenic lymphocytes from infected mice were assessed to unfractionated M. corti supernatants as well as the 70- and 60-kDa stress protein homologs isolated from supernatants. Lymphocytes from infected mice respond to complete supernatant and both of the isolated p70 and p60 stress protein homologs. In addition, supernatant from M. corti cultures stimulates an in vitro antibody response restricted to IgM and IgG1; the same isotypes induced during infection. These results suggest that stress proteins play an integral part in the immune response to M. corti and the associated isotype restriction.
Granulomatous hypersensitivity to Schistosoma mansoni egg antigens in human schistosomiasis. II. In vitro granuloma modulation induced by polyclonal idiotypic antibodies.
Authors: Parra J C , Gazzinelli G , Goes A M , Moyes R B , Rocha R , Colley D G , Doughty B L 
Published: December 2022

Abstract
We have previously reported on Id/anti-Id-receptor interactions in clinical human schistosomiasis. These findings support a hypothesis that anti-SEA cross-reactive Id develop in some patients during the course of a chronic infection and participate in regulation of anti-SEA cellular immune responses. We report here on experiments that extend those observations to the regulation of granulomatous hypersensitivity measured by an in vitro granuloma model. T cells from chronic intestinal schistosomiasis patients were stimulated in vitro with anti-SEA Id and assayed in an autologous in vitro granuloma assay for modulation of granuloma formation. These anti-SEA Id-reactive T cells were capable of regulating autologous in vitro granuloma formation. Both CD4 and CD8 T cells could be activated to regulate granuloma formation. This regulatory activity, initiated with stimulatory anti-SEA idiotypic antibodies, was antigenically specific and was dependent on the presence of intact F(ab')2 Ig molecules. The ability to elicit this regulatory activity appears to be dose dependent and is more easily demonstrated in chronically infected intestinal patients or SEA-sensitized individuals. These data support the hypothesis that anti-SEA cross-reactive Id are important in regulating granulomatous hypersensitivity in chronic intestinal schistosomiasis patients and these cross-reactive Id appear to play a major role in cell-cell interactions that result in the regulation of anti-SEA cellular immune responses.
Functional analysis of a T cell line specific for antiidiotypic antibodies to a Schistosoma mansoni protective epitope. I. Role in the anti-S. mansoni antibody response.
Authors: Velge-Roussel F , Auriault C , Mazingue C , Capron A 
Published: December 2022

Abstract
Previous data have shown that from an antiparasitic IgE mAb (mAb1), antianti-Id IgG and IgE antibodies (Ab3) could be prepared. These Ab3 demonstrated the same functional properties as the Ab1, such as in vitro cytotoxic activity toward schistosomula and in vivo a protective effect against Schistosoma mansoni infection. To study the possible interactions between the idiotypic network and the regulation of isotypic expression, we focused on Id-specific T cells obtained by immunization with Ab2. Both Ab2 idiotopes and native schistosomula Ag were able to stimulate the proliferation of anti-Ab2 T cells in vitro. The activation of anti-Ab2 T cells by Ab2 shared the classic characteristics of Th cells, namely, it was MHC-restricted and required APC. A T cell line could be maintained in long term culture by stimulation with schistosomula Ag. The adoptive transfer of cells from this line to 26-kDa Ag-immunized or S. mansoni-infected rats led to a dramatic increase in the specific humoral response. This effect was restricted to antibodies specific for 26- and 56-kDa Ag (the targets of the mAb1) and was observed for the two isotypes tested, i.e., IgG and IgE. Finally, the helper effect on the antibody response could be further amplified by cooperation of anti-Ab2 T cells with Id-specific cells of the first generation (anti-Ab1 cells). Together with Ag-specific Th cells, the Id-specific T cells may, due to their specificity and their functional properties, play a major role in the induction and more importantly, in the maintenance of the immune response.
Functional analysis of a T cell line specific for antiidiotypic antibodies to a Schistosoma mansoni protective epitope. II. Induction of protective immunity in experimental rat schistosomiasis.
Authors: Velge-Roussel F , Auriault C , Damonneville M , Capron A 
Published: December 2022

Abstract
In our previous work on the idiotypic network in the rat model of schistosomiasis we showed that immunization with an IgE mAb specific for 26/56-kDa parasitic Ag resulted in the production of anti-anti-Id antibodies of both the IgG and IgE classes. Further studies demonstrated that anti-Ab2 T cell lines, obtained by immunization with Ab2 antibodies, functioned as conventional Th cells; they were MHC-restricted and required APC to proliferate in the presence of the native schistosomula Ag and the Ab2 antibodies. We report the involvement of these anti-Ab2 cells in the regulation of protective immunity. The transfer of long term culture anti-Ab2 T cell lines into LOU/M rats, followed by a challenge infection by Schistosoma mansoni 1 day after the cell transfer led to a slight increase in the worm burden. On the contrary, the transfer of anti-Ab2 T cells 90 days before S. mansoni infection induced a significant reduction of the worm burden (up to 57%). T cells recovered from the protected rats were stimulated by the native schistosomula Ag as well as by tryptic fragments of IgG isolated from the Ab2 sera, in the presence of irradiated thymic cells as APC. We also analyzed the humoral response developed by the rats after transfer with the anti-Ab2 T cell lines. The sera induced various inflammatory cells into cytotoxic effectors against the larvae of S. mansoni, arguing for the presence of functional IgE in the sera. Moreover, when these sera were passively transferred into rats infected 1 day later, a significant reduction of the worm burden was observed. However, antibody-dependent cytotoxic mechanisms efficient 10 days after the anti-Ab2 T cell transfer did not correlate with the protective immunity which required a 90-day delay to be established. These data suggest that the protective immunity induced by the anti-Ab2 cells is supported both by the cellular and humoral components and that in a future vaccinating strategy the idiotypic network may play a crucial role.
Bispecific anti-idiotype/anti-CD3 antibody therapy of murine B cell lymphoma.
Authors: Weiner G J , Hillstrom J R 
Published: December 2022

Abstract
Retargeting of T cells by bispecific IgG which binds to both CD3 and a tumor-associated Ag can induce T cell lysis of target cells irrespective of TCR specificity. The current studies were designed to further explore the efficacy and specificity of bispecific IgG-directed therapy in an immunocompetent animal model, and to evaluate the mechanisms responsible for bispecific IgG-directed inhibition of tumor cell growth by using the 38C13 murine lymphoma system. In vitro, proliferation of activated T cells in the presence of bispecific IgG was increased when the relevant, but not the irrelevant target cells were present. Bispecific IgG specifically induced activated T cell mediated lysis of cells expressing the target Ag, but not of cells expressing an irrelevant Ag, even when the irrelevant cells were in the same cell mixture, indicating contact between target cells and T cells plays a major role in bispecific IgG-mediated lysis. Bispecific IgG was less effective than anti-Id at inducing target cell lysis when peritoneal macrophages were used as effectors, suggesting bispecific IgG Fc is not responsible for cytotoxicity in this system. In vivo, bispecific IgG was significantly superior to anti-Id, anti-CD3, or a combination of anti-Id and anti-CD3 in preventing tumor growth in immunocompetent mice inoculated with syngeneic lymphoma. Phenotypic evaluation of tumors that emerged despite therapy indicated bispecific IgG selects for the emergence of Id variant lymphoma cells. In separate studies, 38C13 tumor inocula containing cells recognized by the therapeutic antibody were supplemented with a small number of 38C13 cells which expressed a distinct Id not recognized by the therapeutic antibody. Untreated mice inoculated with this mixture developed tumors containing cells of both phenotypes, whereas tumors emerging from mice treated with bispecific IgG contained only cells expressing the nonreactive Id. These studies demonstrate bispecific IgG-directed lysis is therapeutically superior to monospecific anti-Id therapy in the 38C13 tumor model, and that tumor lysis is mediated largely by cell-cell contact. As with other forms of anti-Id based therapy, Id variants can emerge as resistant cell populations after bispecific IgG therapy.
Reduction of disulfide bonds within lysosomes is a key step in antigen processing.
Authors: Collins D S , Unanue E R , Harding C V 
Published: December 2022

Abstract
Reduction of disulfide bonds is a key step in antigen processing both to allow the unfolding of protein antigens, increasing the access of proteolytic processing enzymes, and to expose free Cys residues within linear peptide epitopes recognized by T cells. We show here that reduction and alkylation of Ag (hen egg lysozyme and ribonuclease A) vastly increased their proteolysis (by specific enzymes or lysosomal fractions) and the production of specific immunogenic peptides that bound to class II MHC molecules recognized by T hybridoma cells. We also show that the lysosome is the vesicular compartment that mediates protein disulfide reduction. We coupled [125I]tyrosine to 131I-alpha 2-macroglobulin or [131I] transferrin via a reducible disulfide linker. Removal of [125I]tyrosine from the alpha 2-macroglobulin conjugate was initiated only after 15 to 20 min of uptake by macrophages, suggesting that reduction occurred late in the endocytic pathway. No reduction of transferrin conjugates was seen, indicating that early, recycling endosomes did not contain reducing activity. Subcellular fractionation showed that the disulfide bonds were reduced only in heavy density (lysosome) fractions and remained intact in fractions of light density (endosomes and plasma membrane). These results indicate the importance of lysosomes in the biochemical processing of protein Ag presented to T cells.
Depletion of mouse alpha beta T cell antigen receptor bearing lymphocytes by neonatal monoclonal antibody treatment.
Authors: Mixter P F , Sydora B C , Hershberg R M , Kronenberg M 
Published: December 2022

Abstract
Neonatal treatment with a monoclonal antibody specific for the alpha beta TCR results in mice with a long term, severe depletion in the number of alpha beta T cells in the periphery. Significant numbers of T cells reappear in the periphery about age 65 days, but these cells tend to lack expression of CD4 or CD8. Splenocytes of antibody-treated mice are less sensitive to mitogen stimulation or stimulation with MHC allogeneic cells. The level of serum IgG but not IgM was decreased by the treatment. Anti-alpha beta TCR antibody treatment decreased single-positive T lymphocytes that express high levels of the CD3/alpha beta TCR complex from the thymus, suggesting that the treatment could act in part by affecting negative selection of alpha beta TCR+ thymocytes. This treatment does not, however, detectably affect either the homing or the numbers of gamma delta T cells which are abundant in the intestinal epithelium, but which remain a minor population in the spleen and lymph nodes. This supports the hypothesis that gamma delta T cells are developmentally autonomous from alpha beta T cells. These mice provide an excellent model system for assessing the developmental and functional role of gamma delta T lymphocytes in vivo.
Proliferation of natural suppressor cells in long-term cultures of spleen cells from normal adult mice.
Authors: Yoshida T , Norihisa Y , Habu S , Kobayashi N , Takei M , Kanehira N , Shimamura T 
Published: December 2022

Abstract
Natural suppressor cells were induced by culturing spleen cells from normal adult mice for 2 to 3 wk. The suppressor cells were large in size, nonadherent and nonspecifically suppressed the plaque-forming cells response of fresh spleen cells to SRBC in vitro. The suppressive activity of the cells was not affected by treatment with indomethacin or anti-Thy-1, anti-Ig, anti-Ia, or anti-asialoGM1 plus complement. Phenotype analysis by FACS showed that Thy-1, L3T4, Ly-2, CD3-epsilon, TCR-alpha beta, Ig, B220, Ia, and asialoGM1 Ag were all absent in the suppressor cells, although they were wheat germ agglutinin receptor positive. The suppressor cells did not demonstrate cytotoxicity against either YAC-1 or P-815 cells. Enriched large cell populations from fresh normal spleens expressed the same phenotypes and also exhibited the suppressive activity. These findings suggest that a minor population of natural suppressor cells exist in the normal adult mouse spleen and they proliferate during the in vitro culture of spleen cells.
Hemorrhage induces enhanced Kupffer cell cytotoxicity while decreasing peritoneal or splenic macrophage capacity. Involvement of cell-associated tumor necrosis factor and reactive nitrogen.
Authors: Ayala A , Perrin M M , Wang P , Ertel W , Chaudry I H 
Published: December 2022

Abstract
Studies indicate that simple hemorrhage produces a profound depression of cell-mediated immunity, thereby contributing to an enhanced susceptibility to septic challenge in the host. However, it remains unknown whether or not the macrophages' cytotoxic capacity is altered after hemorrhage. To study this, C3H/HeN mice were bled to and maintained at a blood pressure of 35 mm Hg for 60 min, and adequately resuscitated. Mice were then killed at 2 or 24 h after hemorrhage to obtain peritoneal macrophage, splenic macrophage, and Kupffer cells. Cytotoxicity was assessed by determining the capacity of these macrophages to lyse [3H]TdR labeled WEHI-164 clone 13 or P815 tumor target cells (WEHI-164, sensitive to both soluble and cell-associated TNF vs P815 cells, insensitive to soluble TNF). Peritoneal and splenic macrophages from hemorrhaged animals exhibited a significantly reduced cytotoxic capacity, whereas Kupffer cells' ability to kill the target cells was enhanced. Similarly, the Kupffer cells' capacity to release TNF and IL-1, as well as express cell-associated forms of this cytokine are significantly enhanced on macrophages isolated 2 h after hemorrhage, whereas peritoneal macrophages are not. Furthermore, antibodies directed at mouse TNF but not against murine IL-1 alpha or murine IL-6 were able to oblate the enhanced target cell lysis of unfixed, as well as paraformaldehyde fixed (metabolically inactive) Kupffer cells. Studies using inhibitors (GN-monomethyl-arginine, superoxide dismutase, catalase, and ibuprofen) of other TNF-inducible mechanisms of target cell killing indicated that only the inhibition of the release of reactive nitrogen consistently depressed the cytotoxic capacity of Kupffer cells from hemorrhaged mice. Thus, the increased Kupffer cell cytotoxicity from hemorrhaged mice is most likely mediated through the expression of cell-associated TNF and the release of reactive nitrogen.
Independent analysis of the 16/6 idiotype lupus model. A role for an environmental factor?
Authors: Isenberg D A , Katz D , Le Page S , Knight B , Tucker L , Maddison P , Hutchings P , Watts R , André-Schwartz J , Schwartz R S 
Published: December 2022

Abstract
The recent description of a lupus-like disease in normal mice after injections of human mAb that bind DNA and carry the common Id 16/6 Id has excited much attention. In an effort to reproduce this model we have performed two experiments using eight human mAb three of which bear the 16/6 Id. Despite using an injection protocol very similar to that of the original authors and waiting for up to 1 yr we were unable to detect any autoantibodies or any evidence of renal disease. We suspect that our failure to reproduce the model may be due to differences in either or both the batches of CFA used, or in the animal house environments. It supports the view that a mosaic of effects is required to induce clinical expression of an autoimmune disease.