bluuebunny/crossref_metadata_2025_split huggingface dataset:
Macrophage cytotoxicity against schistosomula of Schistosoma mansoni involves arginine-dependent production of reactive nitrogen intermediates.
Authors: James S L , Glaven J 
Published: December 2022

Abstract
Lymphokine (LK)-activated macrophages are cytotoxic for multicellular larvae of the helminth parasite Schistosoma mansoni. Macrophage-mediated larval killing was found to be arginine dependent, as indicated by inhibition in the presence of exogenous arginase or the competitive inhibitor NG-monomethyl-L-arginine. Culture supernatant fluids from the larvicidal LK-activated macrophages contained nitrite, a product of activated macrophages derived by oxidation of arginine and implicated in the antitumor and antimicrobial effector function of these cells. Nitrite was not detectable in supernatant fluids obtained from nonactivated macrophages or from macrophages stimulated with LK in the presence of arginase or NG-monomethyl-L-arginine. Addition of excess iron or the reductant sodium dithionite to LK-activated macrophage cultures also inhibited larval killing in vitro, under conditions that have been shown by others to stabilize the activity of iron-containing enzymes involved in respiration. Nitrite production was not decreased under these conditions. These observations are consistent with the hypothesis that macrophage-mediated schistosomulum killing is caused, at least in part, by a mechanism proposed for tumor cytotoxicity, whereby production of reactive nitrogen intermediates triggers iron loss from critical target cell enzymes leading to lethal metabolic inhibition. In accordance, schistosomula were shown to be killed by inhibitors of mitochondrial respiration.
The PSA-2 glycoprotein complex of Leishmania major is a glycosylphosphatidylinositol-linked promastigote surface antigen.
Authors: Murray P J , Spithill T W , Handman E 
Published: December 2022

Abstract
Polyclonal rabbit antiserum to the Triton X-114 phase material of Leishmania major, which comprises the surface and internal integral membrane proteins of the parasite, was used to screen a lambda gt11 genomic expression library. A recombinant clone producing a Mr 123,000 beta-galactosidase fusion protein was isolated. Antibodies affinity-purified on this fusion protein recognized a complex of three surface-oriented proteins of promastigotes of L. major of Mr 94,000, 90,000, and 80,000 that we have termed the promastigote surface Ag 2 (PSA-2) complex. The DNA sequence of the insert in this clone predicted the 3' end of an open reading frame encoding a hydrophobic C-terminus. The inferred C-terminal sequence was suggestive of a glycosylphosphatidyl-inositol membrane anchoring mechanism. Phosphatidylinositol-specific phospholipase C treatment of the native PSA-2 proteins caused a shift in their electrophoretic mobility with an apparent reduction in the molecular weight of the PSA-2 complex. After phospholipase C treatment these proteins also displayed the cryptic cross-reacting determinant recognized by antibodies to the Trypanosoma brucei variant surface Ag. Moreover, PSA-2, which previously partitioned in the detergent phase after Triton X-114 phase separation, became water-soluble after phospholipase C treatment. Immunoprecipitation of the PSA-2 proteins with sera directed to lectin-binding proteins indicated that these polypeptides may be differentially glycosylated. Finally, these PSA-2 proteins were recognized by sera from some patients with cutaneous leishmaniasis.
A second sequence element located 3' to the NF-kappa B-binding site regulates IL-2 receptor-alpha gene induction.
Authors: Pomerantz J L , Mauxion F , Yoshida M , Greene W C , Sen R 
Published: December 2022

Abstract
Transcriptional induction of the gene encoding the alpha-subunit of IL-2R has been shown to be mediated by a sequence element (GGGGAATCTCCC) that is homologous to the NF-kappa B-binding site of the kappa Ig gene enhancer. In this report we demonstrate that the induced transcription of this gene by mitogen and by the tax gene product of the type-I human T cell leukemia virus is dependent upon an additional sequence motif (GGGCGTAGC) located approximately 10 bp downstream of the previously identified site. This newly identified motif binds a factor that is present in extracts derived from different cell types and does not appear to be required for basal promoter activity. We conclude that proteins binding at both sites act coordinately, leading to maximal induction of the receptor gene.
Tumor growth in vivo selects for resistance to tumor necrosis factor.
Authors: Lattime E C , Stutman O 
Published: December 2022

Abstract
The relationship between in vivo tumor growth and resistance to TNF in WEHI-164 cells has been examined. When a highly TNF-sensitive clone of WEHI-164 was grown in vivo in syngeneic mice it became resistant to rTNF such that a 4 to 5 log higher concentration of TNF was required to produce tumor lysis in vitro. When compared with an in vitro selected TNF-resistant variant, the in vivo selected line was significantly more tumorigenic. The resistant phenotype of both the in vivo and in vitro selected variants was stable in culture and both selected lines were also resistant to lysis by syngeneic spleen cells with natural cytotoxic activity. The parental clone and the two variants were equally sensitive to lysis by allo-CTL and expressed similar levels of MHC class I Ag. Resistance to TNF in the two variants was not a function of de novo production of TNF measured as supernatant TNF activity or TNF mRNA expression. These studies are the first to demonstrate that in vivo tumor growth results in resistance to TNF and therefore may have direct relevance to the efficacy of TNF in the treatment of human neoplasms.
Neonatal suppression with anti-Ia antibody. III. In vivo responses to the type 2 antigen TNP-Ficoll.
Authors: Fultz M , Carman J , Finkelman F D , Mond J J 
Published: December 2022

Abstract
We studied the response to thymus-independent type 2 (type 2) Ag in mice suppressed from birth with anti-Ia antibody. Although these mice have significantly reduced numbers of surface IgM+ cells and reduced or absent levels of Ia-restricted Th cell activity, their IgM antibody response to the type 2 Ag TNP-Ficoll was unaffected whereas that to the prototypic thymus-dependent Ag SRBC was predictably eliminated. These data suggest that an in vivo antibody response can be made to type 2 Ag in the absence of Ia-dependent cellular interactions. The surface IgM+IgD-Ia- B cells that are found in the anti-Ia antibody-suppressed mouse may represent an expanded population of Ia-independent, type 2 Ag-sensitive B cells normally present as a smaller proportion of the splenic lymphocyte population. Thymus-dependent responses, which have been shown to have an absolute requirement for an Ia-dependent interaction, are absent in these animals.
IL-1 induces high affinity IL-2 receptor expression of CD4-8- thymocytes.
Authors: Falk W , Männel D N , Darjes H , Krammer P H 
Published: December 2022

Abstract
We investigated the role of cytokines for the growth of CD4-8-thymocytes (double negative thymocytes) (DNT) in vitro and found that IL-1-induced IL-2-dependent proliferation of only the IL-2R-positive DNT subpopulation. The presence of IL-1 during the first 18 h of culture was sufficient for an optimal response and suggested that IL-1 induced DNT differentiation. We could indeed show by RNA dot blot analysis that IL-1 stimulated de novo expression of the p55 chain of the IL-2R thus initiating high affinity IL-2 binding and a proliferative response. Because macrophages and epithelial cells in the thymus produce IL-1 we propose that IL-1 is involved in early events during maturation of immature thymocytes.
Site-specific antibodies distinguish single amino acid substitutions in position 57 in HLA-DQ beta-chain alleles associated with insulin-dependent diabetes.
Authors: Atar D , Dyrberg T , Michelsen B , Karlsen A , Kofod H , Mølvig J , Lernmark A 
Published: December 2022

Abstract
The HLA-DQ beta-chain gene shows a close association with susceptibility or resistance to autoimmune insulin-dependent diabetes mellitus (IDDM) and it has been suggested that the amino acid in position 57 may be of pathogenetic importance. To study the expression of the IDDM associated HLA-DQ beta-chain alleles, we immunized rabbits with 12 to 13 amino acid long peptides representing HLA-DQw7 and -DQw8 allelic sequences, differing only by one amino acid in position 57 being aspartic acid (Asp) and alanine (Ala), respectively. Immunoblot analysis of lymphoblastoid cells showed that several antisera recognized a 29-kDa protein, equivalent to the expected molecular size of the HLA-DQ beta-chain to yield two antisera specific for HLA-DQw7 (pos. 57Asp) and three antisera for HLA-DQw8 (pos. 57Ala) positive cells. Analysis of HLA-DR 3/4 positive IDDM patients (n = 24) and controls (n = 19) showed that all (100%) patients were positive for pos. 57Ala antiserum compared to 13 of 19 (68%) of the controls. The remaining six controls reacted with the pos. 57Asp antisera, whereas none of the patients did. We have therefore successfully been able to generate site-specific antibodies that distinguish single amino acid substitutions in predetermined positions of allelic HLA-DQ beta-chain gene products. Such sera should become useful to detect and investigate HLA associated susceptibility to autoimmune diseases in man.
Molecular analysis and fine specificity of antibodies against an organophosphorus hapten.
Authors: Buenafe A C , Makowski F F , Rittenberg M B 
Published: December 2022

Abstract
We have identified four fine specificity groups reactive with the organophosphorus hapten Soman among 46 hybridomas generated in specific response to immunization with Soman-keyhole limpet hemocyanin (KLH). The different fine specificity groups do not appear to correlate with the use of particular V genes. Molecular analysis of VH genes demonstrates predominant use of VH J558 family members in hybridomas of all fine specificity groups although several different VH genes within this family as well as others are able to contribute. Diversity of VH gene usage was also apparent in primary IgM-producing hybridomas. In contrast, there appears to be restricted L chain usage; a large number (18/46) used the V kappa 1 family. Interestingly, the V kappa 1 family also plays an important role in the memory response to phosphocholine (PC)-KLH, a related organophosphate hapten which shares several structural features with Soman, particularly when coupled to protein carriers. The V kappa 1 C gene appears to predominate in the PC-KLH response. Restriction analysis of DNA from the V kappa 1-positive Soman-KLH-specific hybridomas suggests that a single V kappa 1 gene may be utilized by 17/18 but that this gene is different from V kappa 1 C and may be V kappa 1 A. We propose that members of the V kappa 1 family contribute favorably in generating combining sites that recognize all or part of the structural features shared by the two haptenic structures Soman and PC when they are coupled to protein. This most likely involves recognition of the phenyl linker moiety as the dominant feature. It appears that the L chain rather than the H chain may play a more significant role in forming the phenyl-Soman-specific combining site and perhaps the combining sites for phenyl or ring structures in general.
Enhancement of human monocyte function against Candida albicans by the colony-stimulating factors (CSF): IL-3, granulocyte-macrophage-CSF, and macrophage-CSF.
Authors: Wang M , Friedman H , Djeu J Y 
Published: December 2022

Abstract
The effect of IL-3, granulocyte-macrophage (GM)-CSF and macrophage (M)-CSF on Candida albicans growth inhibition by human peripheral blood monocytes was investigated. By using a radiolabel microassay developed in our laboratory that makes use of the incorporation of [3H]glucose into residual C. albicans, we demonstrated that rGM-CSF and rIL-3 effectively enhanced human monocyte-mediated anticandidal activity. Incubation for 24 h with either GM-CSF or IL-3 significantly enhanced monocyte antifungal responses down to 0.01 U/ml. M-CSF, at higher concentrations of 10 U/ml, could also enhance monocyte function but to a smaller degree. None of the CSF interfered directly with fungal growth, even up to 1000 U/ml. Because IFN-gamma is also a known monocyte activator, its effect on monocytes was also assessed. Monocytes were first cultured in medium for several days and then further incubated with each of the cytokines. Monocytes aged in medium were found to lose their spontaneous anticandidal activity. Such aged monocytes did not develop anticandidal activity in response to IFN-gamma but did in response to GM-CSF or IL-3. To further elucidate this difference, fresh monocytes were continuously cultured with or without cytokines for 1 to 5 days before assessing their anticandidal activity. Monocytes cultured in IFN-gamma progressively lost their activity by 2 days but monocytes in GM-CSF or IL-3 maintained their high level of anticandidal activity throughout the whole length of culture. Therefore, GM-CSF and IL-3 not only enhanced fresh monocyte anticandidal activity, but maintained monocyte function for a longer period. These results suggest that GM-CSF and IL-3 may act on monocytes via a different pathway than does IFN-gamma.
Lymphocytes generated by in vivo priming and in vitro sensitization demonstrate therapeutic efficacy against a murine tumor that lacks apparent immunogenicity.
Authors: Shu S Y , Chou T , Sakai K 
Published: December 2022

Abstract
The adoptive transfer of sensitized lymphocytes is an effective means to mediate the regression of established tumors. However, successful therapy can only be demonstrated in animal models where tumors are intrinsically immunogenic, capable of eliciting systemic immunity. To explore the potential of this therapeutic approach to tumors of less immunogenicity, we have selected and used a murine tumor, MCA 102, for the current study because all attempts to immunize syngeneic mice failed. We report here that inoculation of mice with a mixture of tumor cells and a bacterial adjuvant, Corynebacterium parvum led to the production of sensitized, but not fully functional, lymphocytes in the draining lymph nodes (LN). These cells, termed pre-effector cells, could nevertheless further differentiate to acquire full immunologic function by an established in vitro sensitization culture method. In adoptive immunotherapy experiments, transfer of as few as 1.5 X 10(7) in vitro sensitized cells not only reduced established pulmonary MCA 102 metastases but also prolonged survival and cured tumors in a majority of the treated animals. In order to elicit pre-effector cells in vivo, inoculation with both tumor cells and C. parvum was essential. Although a broad range of numbers of MCA 102 tumor cells appeared to be effective, generation of pre-effector cells was dependent on the dose of C. parvum. We have found that a C. parvum dose of 25 micrograms was optimal, whereas higher doses of the adjuvant had suppressive effects. Analysis of the kinetics of their appearance revealed that the generation of pre-effector cells was transient. They were detectable 7 days after in vivo priming followed by a rapid decline. Furthermore, pre-effector cells were detected only in the regional draining LN. No reactivity was demonstrable in the spleen, mesenteric LN, PBL, or bone marrow. Taken together, these results expand the scope of immunotherapy by demonstrating the feasibility of manipulating a limited and obscure immune response to the MCA 102 tumor for therapeutic efficacy.
Feline cytotoxic large granular lymphocytes induced by recombinant human IL-2.
Authors: Tompkins M B , Pang V F , Michaely P A , Feinmehl R I , Basgall E J , Baszler T V , Zachary J F , Tompkins W A 
Published: December 2022

Abstract
Large granular lymphocytes (LGL) have been characterized phenotypically and functionally as cytotoxic T lymphocytes, NK cells or lymphokine-activated killer cells. The most prominent morphologic feature of LGL is large cytoplasmic granules that are thought to contain the molecules responsible for cell lysis. In this study, we describe the morphologic and functional characteristics of IL-2-dependent cytotoxic lymphocytes derived from feline PBL. Stimulation of feline PBL with Con A followed by culturing in 50 U of gibbon monkey IL-2 human rIL-2 induced long term lymphocyte cultures. These lymphocytes are cytotoxic for the feline leukemia virus-induced T cell lymphoma (FL74), in a 4-h 51Cr release assay. All cell lines are either constitutively cytotoxic for FL74 cells, or cytotoxic in a lectin-dependent cell cytotoxic assay, the latter being a characteristic of low passage cultures. In contrast, no cell lines express self lysis or lysis for other lines. [3H]TdR uptake showed that 1 U of human rIL-2 produces a 50% maximal proliferative response by feline lymphocytes suggesting a high degree of homology between the ligand binding sites of feline and human IL-2R. Feline cytotoxic lymphocytes possess abundant cytoplasm containing large azurophilic granules characteristic of LGL. These granules are bound by a bilipid membrane and contain numerous smaller membrane-bound vesicles 50 to 60 nm in diameter. A model is proposed, whereby subsequent to binding of LGL to target cell the large granules fuse to the LGL plasma membrane and release the small vesicles into the binding pocket. The vesicles then transport the lytic molecules directly and selectively to the target cell membrane.
Immunomodulatory activity of staphylococcal enterotoxin-B. The induction of an I-J-restricted suppressor factor.
Authors: Taub D D , Lin Y S , Hu S C , Rogers T J 
Published: December 2022

Abstract
Staphylococcal enterotoxin-B (SEB), a common cause of food-borne intoxication, is a potent polyclonal T cell activator. Previous studies from this laboratory and others have shown that SEB has the capacity to nonspecifically inhibit antibody responses both in vivo and in vitro. We have shown that the inhibitory activity of SEB is mediated, in part, by the activation of a CD8+, CD4-, and CD5- suppressor cell population. The present studies show that the activity of the SEB-induced suppressor cell population is mediated by a soluble factor. This factor nonspecifically inhibits both primary and secondary in vitro antibody responses. Delayed addition analysis demonstrates that the factor must be present early in the ongoing antibody response to exhibit suppressive activity. Monoclonal anti-I-J antisera block the activity of the factor, and eluates (but not filtrates) collected from monoclonal anti-I-J immunoaffinity columns possess suppressive activity. Furthermore, the activity is restricted at the "I-J" gene locus, but is not restricted at the Igh locus. Finally, size-exclusion chromatographic analysis shows that the factor possesses an apparent Mr of 26 kDa. These studies suggest that SEB induces the production of a suppressive factor with properties similar to those exhibited by Ag-induced, and typically Ag-specific, suppressor factors.
The immune response and the eye. III. Anterior chamber-associated immune deviation can be adoptively transferred by serum.
Authors: Ferguson T A , Hayashi J D , Kaplan H J 
Published: December 2022

Abstract
After the anterior chamber (AC) injection of trinitrophenol-coupled (TNP) spleen cells, it is observed that systemic delayed-type hypersensitivity responses to TNP are inhibited by Ag-specific suppressor T cells. We recently reported that suppression is initiated by viable TNP-coupled T cells within the inoculum and upon further analysis we found that these cells have the surface phenotype of CD4+ Ts inducer cells. We report here that treatment of these TNP-T cells with cycloheximide or cytochalasin-B before to AC injection abolishes suppression, whereas treatment with 2000 rad radiation does not. This indicates that protein synthesis and secretion are required to initiate suppression but proliferation is not. Further, we demonstrate the adoptive transfer of suppression by serum of AC inoculated animals. Detection of the component in serum in adoptive transfer assays, however, requires removal of the spleen before AC injection. We establish that the material in serum is a Ts cell product (T suppressor-inducer factor) based on three criteria: it is Ag specific, genetically restricted, and reactive with a mAb that specifically identifies these molecules. These results suggest that the signal leaving the eye to induce suppression of delayed-type hypersensitivity is T cell derived and that molecules mediating immune regulation for this organ are made within the eye and transported via the serum to the spleen.
Involvement of class II MHC molecules in the LPS-induction of IL-1/TNF secretions by human monocytes. Quantitative differences at the polymorphic level.
Authors: Santamaria P , Gehrz R C , Bryan M K , Barbosa J J 
Published: December 2022

Abstract
Anti-class II ag mAb (DR and DQ) inhibited, in a dose-dependent manner, LPS-induced IL-1 and TNF secretions from human monocytes (34 to 95% inhibition). The potentiating effect of IFN-gamma on LPS-induced TNF secretion (15.3 +/- 0.7 to 44 +/- 0.6 ng/ml) was also blocked by anti-class II ag mAb (44 +/- 0.6 to 0.3 +/- 0.03 ng/ml). We also report a relationship between interindividual differences in monocyte IL-1 and TNF secretions and the HLA-D-encoded genetic polymorphism. Heterozygotes were, in general, higher secretors of those cytokines than homozygotes. Analysis of these secretions in heterozygotes demonstrated a differential effect of certain haplotype combinations (i.e., DR2-DR4 vs DR2-DR3) that could be arbitrarily characterized as being "low" or "high" secretors (6,230 +/- 2,950 vs 13,029 +/- 6,541 cpm for IL-1, and 12 +/- 10 vs 25 +/- 15 ng/ml for TNF, p = 0.006 and 0.048). DR-associated Dw subtypes appeared to account for differences within certain haplotype combinations (Dw18 vs Dw19 in DRw13/DR4) (11,227 +/- 3,648 vs 17,166 +/- 3,176 cpm for IL-1, and 13 +/- 9 vs 25 +/- 10 ng/ml for TNF, p = 0.02 and 0.047). Interindividual differences were better explained by differences in LPS sensitivity than by differences in the kinetics of secretion and related not to the secretory process itself but to the rate of cytokine synthesis. Finally, there were no relationships between high secretor genotypes and IDD high risk genotypes. Thus, we conclude that, a) LPS-induced IL-1 and TNF secretions are, at least in part, regulated by class II MHC molecules, b) that HLA-D region-encoded genetic polymorphism accounts for interindividual differences in these secretions, and c) that the HLA-associated risk to develop IDD is not explained by these cytokine secretory differences as previously proposed.