bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of class II MHC molecules on human endothelial cells. Effects of IFN and dexamethasone.
Authors: Manyak C L , Tse H , Fischer P , Coker L , Sigal N H , Koo G C 
Published: December 2022

Abstract
Human vascular endothelial cells normally do not express class II MHC molecules in culture. IFN-gamma has been shown to induce expression of class I and class II MHC molecules on endothelial cell cultures from umbilical cord. We could detect these Ag by FACS analysis when endothelial cells were cultured for 3 days in the presence of 200 to 1000 U/ml of rIFN-gamma. Among the class II MHC molecules, HLA-DR and -DP but not -DQ were consistently induced. Addition of rIFN-alpha-D/A to IFN-gamma-treated cells inhibited the expression of class II MHC but not class I MHC molecules. Furthermore, the inhibition was more pronounced when IFN-alpha-D/A was added before or simultaneously as IFN-gamma. Natural IFN-alpha also exhibited similar inhibition and its suppressive effect was abolished in the presence of anti-IFN-alpha antibody. On the contrary, dexamethasone, a known inhibitor of class II MHC molecules on murine macrophages, showed a slight enhancing effect on class II MHC Ag. These results suggest an immunoregulatory role for IFN-alpha on non-lymphoid cells and that controlling elements for expression of class II MHC molecules may be different on various cell types as well as species.
Demonstration by in situ hybridization of dissimilar IL-1 beta gene expression in human alveolar macrophages and blood monocytes in response to lipopolysaccharide.
Authors: Bernaudin J F , Yamauchi K , Wewers M D , Tocci M J , Ferrans V J , Crystal R G 
Published: December 2022

Abstract
IL-1 beta is the major form of IL-1 produced by mononuclear phagocytes. To evaluate the possible mechanisms underlying the observation that mature populations of human mononuclear phagocytes as alveolar macrophages are relatively poor IL-1 producers compared with blood monocytes, the expression of the IL-1 beta gene mRNA transcripts was evaluated in LPS-stimulated normal autologous blood monocytes and alveolar macrophages by using a IL-1 beta cDNA probe. Although Northern analysis demonstrated that stimulated monocytes and alveolar macrophages both express 1.8-kb IL-1 beta mRNA transcripts, cytoplasmic dot blot analysis showed that the total IL-1 beta mRNA content in alveolar macrophages was only 38 +/- 5% of that in blood monocytes. In situ hybridization with antisense and sense IL-1 beta RNA probes demonstrated that whereas most of stimulated blood monocytes contained IL-1 beta mRNA transcripts, a significant proportion of autologous alveolar macrophages stimulated in an identical fashion did not express the IL-1 beta gene. Within 4 h after LPS stimulation, IL-1 beta mRNA transcripts were detected in 81 +/- 6% monocytes, whereas only 16 +/- 9% of alveolar macrophages were positive, and by 18 h this had increased only to 43 +/- 15%. Quantification of the size distribution of the IL-1 beta mRNA expressing mononuclear phagocytes demonstrated that, among the population of alveolar macrophages, the cells expressing this gene were not confined to those that were "monocyte-like." These observations demonstrate that there is a heterogeneity among population of mononuclear phagocytes in their ability to express the gene for IL-1 beta, which could explain the differences observed in IL-1 production.
Comparative biochemical and tissue distribution study of four distinct CD45 antigen specificities.
Authors: Pulido R , Cebrián M , Acevedo A , de Landázuri M O , Sánchez-Madrid F 
Published: December 2022

Abstract
Studies on the antigenic structure of the human CD45 glycoproteins using mAb have revealed the existence of four reactivity patterns defined specifically by distinct biochemical, cellular, and histochemical distributions. In addition to the two well characterized Ag specificities, CD45 and CD45R, present on the four glycoproteins (220, 205, 190, and 180 kDa) and on the 220-kDa member, respectively, we have identified two novel specificities. These have been defined by two different mAb, UCHL1 and PD7/26/16, that recognize an epitope exclusively expressed on the 180-kDa lowest molecular sized polypeptide and an epitope shared by the three higher molecular sized polypeptides (220, 205, 190 kDa) of the complex, respectively. It has been demonstrated that they are also part of the CD45 complex by immunoprecipitation, immunoblotting, and binding assays with purified CD45 molecules. Comparative analysis by flow cytometry and immunoperoxidase techniques also showed a distinct pattern of cell distribution for each specificity. The 180-kDa specificity is present on a subset of T cells but absent on B lymphocytes, whereas the 220-kDa specificity is mainly expressed by B cells and a subpopulation of T lymphocytes. On the other hand, the cell distribution of the epitope common to the three higher members is slightly different to the conventional pan-leukocyte CD45 specificity. Thus, certain CD45+ cell types such as cutaneous Langerhans' cells, sinusoidal lymph node macrophages, and a small subset of T cells in both lymph node and tonsil did not express the 220/205/190-kDa specificity. These results further support that CD45 glycoproteins constitute a very heterogeneous molecular complex with epitopes that are selectively expressed by different cell types and by T cells at different stages of maturation.
Assessment of IgE-receptor function through measurement of hydrolysis of membrane inositol phospholipids. New insights on the phenomena of biphasic antigen concentration-response curves and desensitization.
Authors: Maeyama K , Hohman R J , Ali H , Cunha-Melo J R , Beaven M A 
Published: December 2022

Abstract
Previous studies have shown that hydrolysis of membrane inositol phospholipids in rat basophilic leukemia (RBL-2H3) cells depended on the rate and extent of the aggregation of receptors of IgE. This response was used as an experimental probe to study the role of IgE receptors in initiating stimulatory and inhibitory processes within the cell. The response was amplified markedly by increasing the concentration of external Ca2+ from 0 to 1 mM, but the concentration required to support half-maximal response varied from less than 0.1 mM for the most potent cross-linking reagent, DNP24BSA (24 molecules of DNP attached to 1 molecule of BSA) to 0.5 mM for the least potent reagent, aggregated OVA. The dependency of phosphoinositide hydrolysis on external Ca2+ was reduced to zero once hydrolysis of inositol phospholipids was underway but secretion of histamine remained totally dependent on the presence of 0.5 to 1 mM external Ca2+. The stimulatory response persisted as long as receptors remained aggregated but it was modulated by a biochemical process, possibly the activation of protein kinase C, that targeted specifically aggregated receptors, or an associated protein. For example, when cells had become desensitized to high concentrations of one Ag, a normal response could be evoked with a second Ag. Also cells that had become desensitized could be reactivated by permeabilizing the cells. Interestingly, bell-shaped Ag dose-response curves, which were characteristic for both the phosphoinositide and secretory responses, were transformed to sigmoid-shaped curves once cells were permeabilized and dialyzed.
Activation of latent rheumatoid synovial collagenase by human mast cell tryptase.
Authors: Gruber B L , Schwartz L B , Ramamurthy N S , Irani A M , Marchese M J 
Published: December 2022

Abstract
The functional role of mast cells in rheumatoid synovium was investigated by assessing the ability of mast cell tryptase to activate latent collagenase derived from rheumatoid synoviocytes. Tryptase, a mast cell neutral protease, was demonstrated in situ to reside in rheumatoid synovial mast cells, by an immunoperoxidase technique using a mouse mAb against tryptase, and in vitro to be released by dispersed synovial mast cells after both immunologic and nonimmunologic challenge. Each rheumatoid synovial mast cell contains an average of 6.2 pg of immunoreactive tryptase and the percent release values of this protease correlated with those of histamine (r = 0.58, p less than 0.01). The ability of purified tryptase to promote collagenolysis was demonstrated in a dose-dependent fashion using latent collagenase derived from rheumatoid synovium, synovial fluid, IL-1-stimulated cultured synoviocytes, and partially purified latent collagenase derived from conditioned media, with between 10 and 92% of the collagen substrate degraded. [3H] Collagen, treated with tryptase-activated latent collagenase, was subjected to electrophoresis on SDS polyacrylamide gels and autoradiography showed the collagen degradation pattern (A, B) characteristically produced by collagenase. Mast cell lysates also activated synovial latent collagenase yielding 24% digestion of collagen substrate. This activator in mast cell lysates could be inhibited by diisopropylflurophosphate or by immunoadsorption of tryptase. Thus, mast cells may activate metalloproteinases and play a role in the catabolism of collagen that occurs in rheumatoid synovium.
Recombinant tumor necrosis factors mediate platelet cytotoxicity to Schistosoma mansoni larvae.
Authors: Damonneville M , Wietzerbin J , Pancré V , Joseph M , Delanoye A , Capron A , Auriault C 
Published: December 2022

Abstract
The involvement of platelets in the immunity directed toward the parasite Schistosoma mansoni has been demonstrated in vitro and in vivo. The killing properties of platelets were shown previously to involve specific IgE after their binding to a membrane receptor. More recently, we have demonstrated that lymphokines released by S. mansoni Ag- or lectin-stimulated CD4+/CD8-T cells were able to induce the platelet cytotoxicity. The isoelectric focusing of the T lymphocyte supernatants showed that two factors were able to stimulate the platelet killing functions. One of them was clearly identified as being IFN-gamma. The present work demonstrates that the second lymphokine was TNF. Indeed the rTNF-beta and, to a lesser extent, rTNF-alpha, induce normal platelets into killer cells for the young larvae of schistosome. Moreover, an additive effect of the TNF-alpha and IFN-gamma has been observed.
Role of L3T4+ and LyT-2+ cells in experimental visceral leishmaniasis.
Authors: Stern J J , Oca M J , Rubin B Y , Anderson S L , Murray H W 
Published: December 2022

Abstract
In contrast to euthymic (nu/+) BALB/c mice, athymic nude (nu/nu) BALB/c mice fail to control the visceral intracellular replication of Leishmania donovani, do not generate the macrophage-activating lymphokine IFN-gamma, and show little or no granulomatous tissue response. To characterize the T cell requirement for successful defense against L. donovani, nude mice were first reconstituted with unfractionated nu/+ immune spleen cells, which readily conferred the capacity to control and eliminate visceral (hepatic) L. donovani. In reconstituted mice, acquired resistance was paralleled by the ability of spleen cells to generate high levels of leishmanial Ag-stimulated IFN-gamma and the development of well formed liver granulomas. In contrast, nude mice reconstituted with either L3T4+- or Lyt-2+-enriched immune spleen cells alone failed to control visceral parasite replication and did not develop effective granulomas despite the finding that transfer of L3T4+ cells largely and Lyt-2+ cells partially restored the capacity to secrete IFN-gamma. To determine whether both T cell subsets were also required in a normal host, nu/+ BALB/c mice were treated with cell-depleting anti-L3T4 and anti-Lyt-2 mAb. Depletion of either T cell subset inhibited the acquisition of resistance to L. donovani and impaired the tissue granulomatous response. Thus, successful T cell-dependent host defense towards intracellular L. donovani and the tissue expression (granulomas) of this mechanism appear to require both L3T4+ and Lyt-2+ cells. A primary role for the L3T4+ cell may be IFN-gamma production; the role of the Lyt-2+ cell and the precise interaction of the two T cell subsets remain to be identified.
IFN-gamma-activated human alveolar macrophages inhibit the intracellular multiplication of Legionella pneumophila.
Authors: Nash T W , Libby D M , Horwitz M A 
Published: December 2022

Abstract
Human alveolar macrophages activated by human rIFN-gamma inhibit the intracellular multiplication of Legionella pneumophila, an intracellular bacterial pathogen and the agent of Legionnaires' disease. Activation of alveolar macrophages with IFN-gamma is dose dependent; significant inhibition of L. pneumophila multiplication (mean 1.60 +/- 0.20 logs) is achieved consistently with concentrations of IFN-gamma of greater than or equal to 2 x 10(-2) micrograms/ml (220 U/ml). Activation of alveolar macrophages is also time dependent. In macrophages treated continuously after explantation, macrophages infected at 48 to 96 h after explantation are more inhibitory than macrophages infected at 24 h after explantation. In macrophages not treated continuously after explantation but treated for various lengths of time before infection, the longer their exposure to IFN-gamma before infection, the greater the inhibition of L. pneumophila multiplication (96 greater than 72 greater than 48 greater than 24 h). IFN-gamma-activated alveolar macrophages exhibit morphologic signs of activation, including increased size, spreading, and aggregation. This paper demonstrates that a human resident macrophage can be activated with IFN-gamma such that it exhibits enhanced antimicrobial activity against a relevant pathogen.
A new murine Ig VH gene family.
Authors: Kofler R 
Published: December 2022

Abstract
A novel murine VH gene family, termed VH10, has been found and characterized. Based on RFLP analysis, this family exhibits extensive polymorphism among inbred strains of mice and encompasses two to five members, depending on the Igh haplotype. Analyses of recombinant inbred strains suggest a map position of this family 5' to the 7183 and Q52 VH gene families. A VH10 gene has been found to encode anti-DNA autoantibodies from lupus mice; another one may be a pseudogene.
Anti-tumor activity of recombinant tumor necrosis factor on mouse fibrosarcoma in vivo and in vitro.
Authors: Tomazic V J , Farha M , Loftus A , Elias E G 
Published: December 2022

Abstract
The experiments presented were designed first to determine the effects of rTNF on the methylcholanthrene-induced fibrosarcoma (FSA-1) in C3H/JSed mice and second to determine whether the observed effects are the result of direct action by rTNF on the tumor or whether rTNF acts as a mediator of other effector mechanisms. Mice received syngeneic FSA-1 fibrosarcoma cells either s.c. or i.v. in order to evaluate growth of transplantable solid tumor or lung metastases, respectively. The range of dosages, from 10(2) to 2 x 10(5) U of rTNF, was administered i.v. at different intervals after the tumor cell injection. Early injection of 10(3) to 10(4) U of rTNF reduced the growth of s.c. injected tumor and the number of lung metastases in i.v. injected mice. In both cases, survival of mice was also prolonged. However, in vitro treatment of FSA-1 tumor cells with rTNF did not result in the reduction of their proliferating activity after injection into mice, although direct cytostatic and moderate cytotoxic activity of rTNF in vitro was demonstrated. To identify whether other cellular mechanisms are involved in the effects observed in vivo, the anti-tumor activity of rTNF-treated spleen cells was evaluated in vitro using a 75Se release assay. Whereas nontreated spleen cells demonstrated very low cytotoxic activity in this system, the cells from rTNF-treated mice showed marked increase in the cytotoxicity against syngeneic tumor cells. These results suggest that the anti-tumor activity of rTNF represents a combination of its direct effect on tumor cells and indirect effects involving host immune mechanisms.
Heterogeneity of lymphokine-activated killer cells induced by IL-2. Separate lymphoid subpopulations lyse tumor, allogeneic blasts, and modified syngeneic blasts.
Authors: LeFor A T , Eisenthal A , Rosenberg S A 
Published: December 2022

Abstract
Murine splenocytes incubated for 3 to 4 days with the lymphokine, IL-2, acquire the ability to mediate the lysis of a wide variety of fresh tumor targets in short term chromium release assays. We undertook these studies to examine the lysis of splenocyte blasts by these lymphokine-activated killer (LAK) cells, to help gain an understanding of the mechanisms of target cell recognition. Allogeneic blast targets but not syngeneic blasts are highly lysable by LAK effector cells. By using congenic mice, we have shown that only the H-2 haplotype, and not other differences, determines the recognition and lysis of a blast target cell. Both Con A- and LPS-induced allogeneic splenocyte blasts are lysed and thus lectin-induced binding of effectors and targets is unlikely to be responsible for this effect. By using in vivo antibody depletion experiments, we showed that different populations of effector cells mediate the lysis of tumor cells and allogeneic blasts. Furthermore, we observed that the lysis of a susceptible blast can be inhibited only by like cold blasts of the same haplotype. These results suggest that there is a separate population of LAK cells responsible for the lysis of each type of blast target cell. Though syngeneic blasts were not lysed by LAK cells, TNP modification of syngeneic blasts converted them into cells that were recognized and lysed by LAK cells. In cold target inhibition studies, the lysis of fresh syngeneic tumor was not inhibited by TNP-modified syngeneic blasts. Similarly, the lysis of TNP-modified syngeneic blasts was not inhibited by fresh tumor. By using in vitro antibody depletion, we determined that TNP-modified blasts are lysed by LAK cells with Thy-1+ precursors, in distinction to the Thy-1- precursors involved in tumor cell lysis. Elimination of the Thy-1+ cells at the precursor stage completely abrogated the lysis of blasts but did not diminish the lysis of tumor cells. We conclude that IL-2 promotes the growth of numerous populations of effector cells with Thy-1+ precursors that have a narrow range of specificity, in contrast to the broad lytic ability for fresh tumor mediated by LAK cells with Thy-1- precursors.
Antibody to a novel 95-kDa surface glycoprotein on human B cells induces calcium mobilization and B cell activation.
Authors: Valentine M A , Clark E A , Shu G L , Norris N A , Ledbetter J A 
Published: December 2022

Abstract
These findings characterize a 95-kDa glycoprotein on the surface of B lymphocytes recognized by the mAb G28-8. This protein (designated Bgp95), previously classified as a CD39 molecule, is unique based on functional, cell distribution, and immunochemical criteria. Biochemical analyses revealed that Bgp95 is a 95-kDa glycoprotein with N-linked carbohydrate and is reduced to about 70-kDa after treatment with endoglycopeptidase F. In functional studies, stimulation by G28-8 mAb or its F(ab')2 fragments induced a G0 to G1 cell cycle transition and was synergistic with PMA, anti-mu, or anti-CDw40 in stimulating proliferation of resting B cells. G28-8 mAb also could induce increases of cytoplasmic free calcium concentration [Ca2+]i in a subpopulation of tonsillar or peripheral blood B cells. The G28-8 mAb alone induced a steady increase in [Ca2+]i detectable even 1 h after stimulation. Cross-linking the G28-8 mAb with a second mAb specific for murine kappa light chains induced a more rapid increase of [Ca2+]i which peaked at 10 to 20 min and then declined. At 1 h after stimulation, [Ca2+]i was higher in B cells stimulated with G28-8 alone than in B cells stimulated with G28-8 plus anti-kappa. The same conditions of cross-linking with the anti-kappa which increased the kinetics of the [Ca2+]i response decreased the proliferative response which otherwise followed co-incubation of the mAb with B cell growth factor or PMA. Thus, conditions leading to rapid but transient [Ca2+]i increase via Bgp95 may not be as effective at stimulating B cell proliferation as conditions favoring a slower prolonged [Ca2+]i response. Although the Bgp95 molecule is present on activated buoyant tonsillar B cells, mAb to Bgp95 did not trigger [Ca2+]i increases in these cells. These results suggest that the Bgp95 protein may function in early B cell activation and that its signal mechanisms are altered by the activation state of the cell.
Fine specificity of murine class II-restricted T cell clones for synthetic peptides of influenza virus hemagglutinin. Heterogeneity of antigen interaction with the T cell and the Ia molecule.
Authors: Mills K H , Burt D S , Skehel J J , Thomas D B 
Published: December 2022

Abstract
We have previously demonstrated diversity in the specificity of murine, H-2k class II-restricted, T cell clones for the hemagglutinin (HA) molecule of H3N2 influenza viruses and have mapped two T cell determinants, defined by synthetic peptides, to residues 48-68 and 118-138 of HA1. In this study we examine the nature of the determinant recognized by six distinct P48-68-specific T cell clones by using a panel of truncated synthetic peptides and substituted peptide analogs. From the peptides tested, the shortest recognized were the decapeptides, P53-62 and P54-63, which suggests that the determinant was formed from the 9 amino acids within the sequence 54-62. Asn54 was critical for recognition since P49-68 (54S) was not recognized by the T cell clones. Furthermore this peptide analog was capable of competing with P48-68 for Ag presentation, thereby suggesting that residue 54 is not involved in Ia interaction and may therefore be important for TCR interaction. Residue substitutions at position 63 also affected T cell recognition, but in a more heterogeneous fashion. Peptide analogs or mutant viruses with a single amino acid substitution at position 63 (Asp to Asn or Tyr) reduced the responses of the T cell clones to variable extents, suggesting that Asp63 may form part of overlapping T cell determinants. However since the truncated peptide P53-62 was weakly recognized, then Asp63 may not form part of the TCR or Ia interaction site, but may affect recognition through a steric or charge effect when substituted by Asn or Tyr. Ag competition experiments with the two unrelated HA peptides, P48-68 and P118-138, recognized by distinct T cell clones in the context of the same restriction element (I-Ak), showed that the peptides did not compete for Ag presentation to the relevant T cell clones, whereas a structural analog of P48-68 was a potent inhibitor. This finding is discussed in relation to the nature of the binding site for peptide Ag on the class II molecule.
Enhancement of suppressor T cell activity by injection of anti-IFN-gamma monoclonal antibody.
Authors: Frasca D , Adorini L , Landolfo S , Doria G 
Published: December 2022

Abstract
In the present study, the contribution of IFN-gamma to the generation of helper activity in mice was investigated by use of anti-mouse IFN-gamma rat mAB (AN 18.17.24). This mAb was alum precipitated and injected i.p. before or after carrier priming. Results show that spleen cell helper activity is markedly inhibited by anti-IFN-gamma mAb injection. This inhibition is time and dose dependent, and counteracted by IFN-gamma administration. Thus, the anti-IFN-gamma mAb appears to inhibit helper cell activity by neutralization of the IFN-gamma required for the antibody response. Moreover, AN 18.17.24 mAb injection results in increased activation of Lyt-2+ T cells which markedly suppress Th activity. These findings altogether indicate that besides the activation of macrophages and Th, IFN-gamma seems to exert a negative interference in suppressor T lymphocyte circuits and, as a consequence, to inhibit immunosuppression.