bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppression of human leukocyte tumor necrosis factor secretion by the serine protease inhibitor p-toluenesulfonyl-L-arginine methyl ester (TAME).
Authors: Scuderi P 
Published: December 2022

Abstract
The addition of the serine protease inhibitor p-toluenesulfonyl-L-arginine methyl ester (TAME) to human peripheral blood mononuclear cells suppressed TNF secretion in a concentration dependent manner. At a concentration 10 mM TAME leukocyte TNF release was completely inhibited without decreasing the secretion of IL-1 alpha. Simultaneously exposing leukocytes to 10 mM TAME and either 1000 U/ml IFN-gamma or 10 micrograms/ml LPS reduced the quantity of TNF secreted by 75% and 47%, respectively, when compared with the effect of either IFN-gamma or LPS alone. TAME was most effective when added to leukocytes at the initiation of culture and the suppressive effects of this protease inhibitor were reversible by washing the cells. TAME suppressed TNF secretion without affecting either the level of TNF mRNA or the expression of cell surface cytokine. These findings suggest that leukocyte TNF secretion is dependent upon the action of one or more serine proteases.
Distinction between immunogenicity and tolerogenicity among HBcAg T cell determinants. Influence of peptide-MHC interaction.
Authors: Milich D R , Jones J E , McLachlan A , Houghten R , Thornton G B , Hughes J L 
Published: December 2022

Abstract
One purpose of this study was to examine the concept of T cell immunodominance employing a neonatal tolerance model. The extent to which a single T cell recognition site can represent the total T cell response to hepatitis B core Ag (HBcAg) was examined in the B10.S and B10 murine strains. It was shown that the entire B10.S T cell response to HBcAg was focused on a single immunodominant site represented by residues 120-131. This was demonstrated by exposing B10.S neonatal mice to p120-140 or p120-131, which resulted in a state of T cell tolerance to the entire HBcAg. In contrast, p120-140 contained an immunogenic T cell site for B10 mice, p129-140, but this site was nontolerogenic. Similarly, injection of p120-140 into (B10.S X B10)F1 neonatal mice resulted in tolerization of p120-131-specific, I-As-restricted T cells, but not of p129-140-specific, I-Ab-restricted T cells. The second purpose of this study was to attempt to explain the immunologic basis of an immunogenic yet nontolerogenic T cell determinant. It was shown that the p120-131 T cell site, which is immunogenic and tolerogenic in B10.S mice, could be converted into an immunogenic/nontolerogenic T cell site by a single amino acid substitution in either residue 127 or 129. Residues 127 and 129 were previously shown to be involved in interaction with MHC class II molecules (agretopic). These results demonstrated that the relative avidity of a peptide-MHC interaction can influence T cell tolerance induction. Furthermore, the results suggest that a higher threshold of peptide-MHC avidity may be required to induce T cell tolerance as compared to the threshold of peptide-MHC avidity required to immunize T cells.
Immunosuppression and transforming growth factor-beta in glioblastoma. Preferential production of transforming growth factor-beta 2.
Authors: Bodmer S , Strommer K , Frei K , Siepl C , de Tribolet N , Heid I , Fontana A 
Published: December 2022

Abstract
Transforming growth factor (TGF)-beta 1 is a polypeptide that is assumed to play a fundamental role in the growth of both normal and neoplastic cells. TGF-beta 2 is a closely related polypeptide, originally described as glioblastoma cell-derived T cell suppressor factor (G-TsF) due to its immunosuppressive activity. Expression of the genes for TGF-beta 1 and G-TsF/TGF-beta 2 was examined in tumor cells and was found to be different in several cell lines and tissues that were tested. Whereas two glioblastoma cell lines expressed both TGF-beta 1 and G-TsF/TGF-beta 2 mRNA, one melanoma and neuroblastoma cell lines showed only TGF-beta 1 mRNA which in the case of the neuroblastoma required cycloheximide treatment for its detection. The coordinate expression of the genes for TGF-beta 1 and G-TsF/TGF-beta 2 in glioblastoma was not paralleled by secretion of both polypeptides as only G-TsF/TGF-beta 2 but not TGF-beta 1 was identified in supernatants of glioblastoma cells. These data provide evidence for a post-transcriptional level of regulation for production of the two forms of TGF-beta. As mRNA for G-TsF/TGF-beta 2 was also identified in fresh surgically removed human glioblastoma tissue, G-TsF/TGF-beta 2 may also be secreted within the tumor in vivo. Unlike glioblastoma, human fetal brain tissues or adult brain specimens studied did not express detectable levels of TGF-beta mRNA. Impaired cell-mediated immunity is an established finding in patients with glioblastoma. Secretion of G-TsF/TGF-beta 2 by tumor cells in vivo may contribute to decreased immune surveillance for tumor development, as well as neovascularization of the tumor tissue.
Natural killer and lymphokine-activated killer cell activities from human marrow precursors. II. The effects of IL-3 and IL-4.
Authors: Keever C A , Pekle K , Gazzola M V , Collins N H , Bourhis J H , Gillio A 
Published: December 2022

Abstract
Both IL-3 and IL-4 have multi-CSF activity on early marrow progenitors. We have examined the effect of IL-3 and IL-4 on the differentiation of NK cells from their marrow-derived precursors and have further examined the interactions of these cytokines with IL-2 and IL-1. We tested marrow which had been depleted of mature cells and of E rosette-positive cells (including NK cells) by treatment with soybean lectin and SRBC (SBA-E-BM). The cytolytic activities of the SBA-E-BM samples were tested in 51Cr-release assays after 7 days of liquid culture. K562 targets were used as a measure of NK activity and NK-resistant Daudi targets were used to measure lymphokine-activated killer (LAK) cell activity. Neither NK nor LAK activity was detectable in marrow cultured in medium without cytokines, or in medium containing IL-3, or IL-4 alone. Both of these cytokines were shown to be inhibitory to the IL-2-induced generation of NK and LAK activity from SBA-E-BM at concentrations as low as 1 U/ml. The inhibitory activity of both IL-3 and IL-4 was found to occur early in the marrow cultures, with little or no inhibitory effects seen if added 48 h after IL-2. IL-3 appeared to be specifically inhibitory to NK cell precursors since addition of IL-3 to cultures of PBMC did not inhibit IL-2-induced lytic activities. In contrast, IL-4 was equally inhibitory to the activation of marrow and peripheral blood NK cells by IL-2. Mixing experiments demonstrated that the reduced lytic activity in IL-3 or IL-4 containing marrow cultures were not due to suppression of the NK effectors, nor could marrow cultured in IL-3 or IL-4 serve as targets for IL-2-activated NK cells. Phenotype analysis of the lymphoid cells in marrow cultures containing IL-2 combined with IL-3 or IL-4 revealed fewer cells expressing Leu-11 (CD16), or Leu-19 (CD56) and fewer CD16, CD56 coexpressing cells compared with marrow cultured in medium containing IL-2 alone. The inhibitory activity of IL-4, but not IL-3, could be partially reversed if IL-1 was added to the cultures, suggesting that IL-1 and IL-4 have opposing activities on NK cells responsiveness to IL-2. These interactions between cytokines might be important in the regulation of NK cell differentiation and on the functional activity of mature NK cells.
Function and regulation of the neutrophil MEL-14 antigen in vivo: comparison with LFA-1 and MAC-1.
Authors: Jutila M A , Rott L , Berg E L , Butcher E C 
Published: December 2022

Abstract
The CD11/18 (LFA-1, Mac-1) molecules participate in neutrophil adhesion to cultured endothelium in vitro and are critical for effective neutrophil localization into inflamed tissues in vivo. More recently, the MEL-14 Ag, which was first defined as a lymphocyte homing receptor, has also been implicated in inflammatory neutrophil extravasation. Here we compare the regulation and function of these adhesion molecules on neutrophils during the in vivo inflammatory response. The MEL-14 Ag is expressed at high levels on bone marrow and peripheral blood neutrophils, but is lost on neutrophils isolated from the thioglycollate-inflamed peritoneal cavity. In contrast, Mac-1 is up-regulated on inflammatory neutrophils and little change is seen in the level of LFA-1 expression. In vitro activation of bone marrow neutrophils with PMA or leukotriene B4 results in a dose dependent increase in Mac-1 and decrease in MEL-14 Ag expression within 1 h after treatment, thus reflecting what is found during inflammation in vivo. Neutrophils activated in vitro or in vivo (MEL-14Low, Mac-1Hi) do not home to inflammatory sites in vivo, correlating with the loss of the MEL-14 Ag and the increased Mac-1 expression. Anti-LFA-1, anti-Mac-1, or MEL-14 antibody given i.v. suppress neutrophil accumulation within the inflamed peritoneum (38%, 30%, and 37% of medium control, respectively) without affecting the levels of circulating neutrophils. However, when FITC-labeled cells are precoated with the mAb and injected i.v., only MEL-14 inhibits extravasation into the inflamed peritoneum (25% of medium control). Finally, in ex vivo adhesion assays of neutrophil binding to high endothelial venules in inflamed-lymph node frozen sections MEL-14 inhibits greater than 90%. anti-LFA-1 20 to 30% and anti-Mac-1 less than 10% of the binding of bone marrow neutrophils to inflamed-lymph node high endothelial venules. These results confirm that both the MEL-14 antigen and Mac-1/LFA-1 are important in neutrophil localization to inflamed sites in vivo, but suggest that their roles in endothelial cell interactions are distinct.
Immunologic significance of diverse specificity of monoclonal antibodies against mannans of Candida albicans.
Authors: Kagaya K , Miyakawa Y , Fujihara H , Suzuki M , Soe G , Fukazawa Y 
Published: December 2022

Abstract
Two agglutinating IgM mAb against mannan Ag of Candida albicans strains were investigated for their specificity. The agglutinating patterns of both mAb with a panel of stationary phase of yeast cells of standard strains did not match those of any known polyclonal antibody (PAb) factors. The reactive patterns of both mAb for a given panel of 202 isolates of seven Candida species and the mode of competitive binding between mAb and a PAb factor, as determined by a combination of direct and indirect immunofluorescence staining, demonstrated that the two mAb were a part of PAb factor 4 (a prescribed reactive pattern of adsorbed PAb) but were different from each other in their specificity. The thereby designated mAb 4b and 4c were tested under PAb factor 4-positive Candida strains and further division into two to three serotypes of each species were made. 1H-Nuclear magnetic resonance spectra (500 MHz) of purified neutral mannans from strains of each serotype showed that although the 1H-nuclear magnetic resonance spectra of mannans from two subtypes of C. albicans serotype A and from each of two serotypes of Candida guilliermondii and Candida glabrata were identical or similar, the two mAb were still able to distinguish their fine determinant structures. Our findings suggest that mAb with entirely identical specificity cannot be produced against even the same determinant groups of mannan. In addition, the fact that microheterogeneity may occur without limit in the mannans of the strains suggests that antibodies with unlimited diverse specificities are produced directed against these antigenic varieties as well.
Surgical stress impairment of murine natural killer cell cytotoxicity involves pre- and postbinding events.
Authors: Pollock R E , Lotzová E , Stanford S D 
Published: December 2022

Abstract
NK cell cytotoxicity may provide an important first line of defense against the implantation of circulating tumor emboli. Previously we reported that murine hind limb amputation induces a rapid and marked impairment of perioperative NK cell cytotoxicity that is associated with increased metastatic activity compared to unmanipulated tumor-bearing controls. Because tumor emboli are systemically discharged in patients undergoing solid tumor resection, we thought it pertinent to begin examining the mechanism underlying the perioperative impairment of murine NK cell cytotoxicity. Studies presented in this report suggest that the mechanism of impairment is multifactorial and includes the surgical stress-induced expansion of splenic erythroblasts that successfully compete with NK cells for YAC-1 target binding sites. In addition, although there is no surgically mediated decrease in splenic NK cell content (as defined morphologically, phenotypically, and functionally), there is an acute decrease in maximal NK cell recycling capacity. An accurate understanding of the mechanisms mediating perioperative impairment of NK cell cytotoxicity may be important in the future development of NK-specific perioperative immunomodulation strategies.
Unrestricted recognition of a nonpeptide antigen by CD8+ cytolytic T lymphocytes.
Authors: Sherman L A , Lara A M 
Published: December 2022

Abstract
CD8+ murine CTL that are specific for an unusual nonpeptide Ag, the heme moiety of hemoglobin, have been derived by in vitro stimulation of spleen cells with hemin. Such CTL demonstrate a requirement for the expression of class I Ag on target cells, yet appear to be unrestricted to the extent that both syngeneic and allogeneic targets precoated with hemin are sensitive to lysis. A series of CTL clones with specificity for hemin was derived from C57BL/6 mice. They exhibited the same type of promiscuous recognition that was observed in CTL populations from a number of different strains. The possibility that hemin acts as a nonspecific mediator of lysis by CTL was ruled out by the fact that a variety of CTL populations and clones specific for different Ag did not exhibit hemin-specific lysis. Some explanations offered to explain these results include 1) the possibility that hemin is recognized by binding to a site on the MHC other than the Ag-binding groove, and 2) the possibility that TCR recognition of a rigid molecule, such as hemin, may be less sensitive to polymorphic variation in the MHC than is recognition of a conventional peptide Ag whose conformation may differ significantly when bound to MHC molecules whose sequences differ within the Ag-binding groove.
IL-6 inhibits lipopolysaccharide-induced tumor necrosis factor production in cultured human monocytes, U937 cells, and in mice.
Authors: Aderka D , Le J M , Vilcek J 
Published: December 2022

Abstract
Incubation of the human U937 histiocytic lymphoma cell line with granulocyte-macrophage colony stimulating factor (GM-CSF) rendered the cells responsive to induction of TNF by LPS. Treatment with IL-6 reduced TNF production in GM-CSF-primed U937 cells. The inhibitory effect was most pronounced (approximately equal to 80%) when IL-6 was added either along with GM-CSF or within the first 3 h of GM-CSF treatment. Both GM-CSF or IL-6 inhibited [3H]TdR uptake in U937 cells, and simultaneous treatment with GM-CSF and IL-6 resulted in an additive inhibitory effect on cell proliferation. However, the inhibition of TNF production could not be explained by the inhibitory effect of IL-6 on cell growth, nor was it due to a reduction in cell viability. An inhibition of TNF production by IL-6 was also demonstrated in cultured human peripheral blood monocytes. Treatment with IL-6 also resulted in a dose-dependent reduction of the 17-kDa TNF band revealed by SDS-PAGE after labeling monocytes with [35S]cysteine and immunoprecipitation with anti-TNF mAb. In addition, treatment with IL-6 resulted in a reduction of monocyte in vitro cytotoxicity for tumor target cells. Finally, in mice sensitized by the administration of Bacillus Calmette-Guérin, the injection of IL-6 significantly reduced the levels of TNF found in the serum upon challenge with LPS. Inasmuch as TNF is known to be an inducer of IL-6, the inhibitory action of IL-6 on TNF production may represent the negative arm of a regulatory circuit. The inhibitory action of IL-6 on TNF production is consistent with a predominantly antiinflammatory role of IL-6 in the intact organism.
A genetically controlled pairing anomaly between HLA-DQ alpha and HLA-DQ beta chains.
Authors: Kwok W W , Thurtle P , Nepom G T 
Published: December 2022

Abstract
The HLA-DQ region contains highly polymorphic alpha and beta loci, so that a diverse set of cis- and trans-associated class II alpha/beta dimers are potentially generated in heterozygous individuals. To evaluate the extent of this predicted diversity, DQ2 beta or DQ3.2 beta cDNA were introduced into a panel of homozygous B cell lines that expressed different DQ alpha alleles. Restricted patterns of alpha/beta pairing were observed in which DQ2 beta and DQ3 beta molecules were unable to pair efficiently with DQ1 alpha chains. This pairing anomaly may contribute to altered class II phenotypes in heterozygous individuals, and is reflected in the absence of either DQ1 alpha, DQ2 beta or DQ1 alpha, DQ3 beta haplotypes in the known human gene pool.
Regulated expression of proenkephalin A in normal lymphocytes.
Authors: Rosen H , Behar O , Abramsky O , Ovadia H 
Published: December 2022

Abstract
The expression of proenkephalin A (PEA), a neuropeptide-encoding gene, was examined in normal rat lymphocytes. With the use of Northern blot hybridization analysis of total RNA, PEA mRNA was found in normal cells derived from spleen, lymph nodes, and bone marrow. Cell sorting of the two main fractions of B and T cells derived from the spleen revealed that PEA is expressed in normal B cells (sIg+). The expression of PEA mRNA was markedly enhanced after a short incubation (3 h) of cells with LPS or Salmonella typhimurium. This was not the case when these cells were incubated with Con A during the same period of time; whereas, in thymocytes the presence of PEA mRNA was exclusively dependent upon mitogenic stimulus (Con A) and could be detected after 24 h of in vitro incubation. Extracts of cells were also found to contain immune reactive enkephalins, indicating that the PEA mRNA is translated. These results support the concept that neuropeptides, such as enkephalins, have a role in the modulation of the immune response and may participate in the bidirectional communication between the nervous and immune systems.
Tumor rejection mediated by transfection with allogeneic class I histocompatibility gene.
Authors: Hui K M , Sim T , Foo T T , Oei A A 
Published: December 2022

Abstract
Non-self class I histocompatibility Ag can act as strong alloantigens and be recognized as distinct targets by CTL. To study the possibility of using allograft rejection to generate tumor-specific immunity, we have introduced an allogeneic class I histocompatibility gene, the H-2Kb gene, into a k haplotype tumor, K36.16, by DNA-mediated gene transfer. The K36.16 tumor grows readily and does not confer protective immunity in AKR mice. A total of 37 H-2Kb-transfected K36.16 clones (Kb/K36.16) was isolated and studied individually. The Kb/K36.16 clones were found to differ significantly in the amount of the exogenous H-2Kb antigens expressed on their cell surface. Moreover, as a result of the transfection, the level of expression of the endogenous H-2Dk Ag was also altered when compared to that of the parental K36.16 tumor cells. All the Kb/K36.16 clones that were positive for the H-2Kb Ag were rejected by the semisyngeneic AKR mice. Moreover, some of these Kb/K36.16 clones were also rejected by syngeneic (AKR x C57BL/10)F1 mice. In consequence of immunization with the Kb/K36.16 clones, the AKR and F1 mice were able to survive a subsequent challenge of the wild-type, unmodified, parental K36.16 tumor cells. More importantly, some of these Kb/K36.16 clones demonstrated an active and specific immunotherapeutic effect, and they were able to eradicate the growth of the parental K36.16 tumor cells in AKR mice. This observation therefore reinforces the feasibility of using DNA-mediated gene transfer as a molecular approach to abrogate tumor growth.
Anti-Ig-stimulated B lymphoblasts can be restimulated via their surface Ig.
Authors: Isakson P C , D'Angelo D , Schetz J , Tardelli L , Puré E 
Published: December 2022

Abstract
Engaging AgR (surface Ig) on B lymphocytes leads to rapid inositol phosphate turnover and elevation of intracellular [Ca2+]. Continuous receptor occupancy (greater than 18 h) by anti-Ig leads to transit of most B lymphocytes from G0 to G1 stage of the cell cycle (blast transformation); a fraction of cells continue into S phase but do not proliferate continuously in the absence of growth factors. Prolonged exposure to ligand can induce receptor desensitization of some receptors. We therefore investigated whether such desensitization occurs in B cells activated by insolubilized anti-Ig. Resting B cells and anti-Ig-activated blasts were examined for their potential to elevate [Ca2+]i, maintain viability, and synthesize DNA in response to reexposure to anti-Ig. B cells and anti-Ig blasts had similar basal [Ca2+]i levels. Anti-Ig blasts retained the capacity to increase [Ca2+]i in response to anti-Ig; the magnitude of the increase was equal to or greater than that observed with resting B cells and occurred in more than 90% of cells. Isolated anti-Ig blasts subcultured in the presence of T cell-derived growth factors for 3 to 5 days responded to restimulation by anti-Ig with an increase in [Ca2+]i similar to that observed in freshly isolated blasts. The B cell and B lymphoblast ion channels were found to be permeable to Ca2+ but impermeable to Mn2+. Finally, blasts restimulated by anti-Ig retained viability and incorporated low levels of [3H]thymidine for 24 h. These results suggest that AgR on activated B lymphocytes can remain functionally coupled to intracellular signaling pathways and can participate in immune responses subsequent to initial activation.
Involvement of IL-6 in mesangial proliferative glomerulonephritis.
Authors: Horii Y , Muraguchi A , Iwano M , Matsuda T , Hirayama T , Yamada H , Fujii Y , Dohi K , Ishikawa H , Ohmoto Y 
Published: December 2022

Abstract
In this study, we demonstrated that IL-6 was a possible autocrine growth factor for rat mesangial cells (MC). rIL-6 induced in vitro growth of rat MC at a concentration of 2 to 200 ng/ml and IL-6 activity was found in the supernatant of cultured rat MC. Northern blot analysis as well as in situ hybridization revealed that IL-6 mRNA was expressed in the cultured MC. Of urine samples from patients with mesangial proliferative glomerulonephritis (PGN) 50% were found to contain significant IL-6 activity (ranging from 30 to 126 pg/ml). Urine samples from other type of primary glomerular diseases such as minimal change nephrotic syndrome or healthy volunteers contained no detectable IL-6 activity. Only 2 of 27 urine samples from membranous nephropathy contained detectable amount of IL-6. Furthermore, there was some relationship between the levels of urine IL-6 and the progressive stage of PGN. Finally, by immunohistochemical staining using an anti-IL-6 mAb, it was shown that MC in the affected glomeruli of PGN patients produced IL-6, whereas MC obtained from the patients with membranous nephropathy, minimal change nephrotic syndrome or normal kidney were not found to produce IL-6. These data suggest that deregulated production of IL-6 is involved in PGN and the measurement of urine IL-6 is helpful for the differential diagnosis of PGN as well as for monitoring the progression of PGN.