bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of tumor-derived cytokines on the immune system of mice bearing a mammary adenocarcinoma. II. Down-regulation of macrophage-mediated cytotoxicity by tumor-derived granulocyte-macrophage colony-stimulating factor.
Authors: Sotomayor E M , Fu Y X , Lopez-Cepero M , Herbert L , Jimenez J J , Albarracin C , Lopez D M 
Published: December 2022

Abstract
Peritoneal elicited macrophages (PEM) from mammary tumor-bearing mice have a decreased capacity to become cytotoxic against syngeneic, allogeneic, and xenogeneic target cells upon in vitro stimulation with LPS, as compared with PEM of normal mice. A regulatory mechanism other than PG release is suggested because the addition of both indomethacin and LPS to macrophage cultures from tumor-bearing mice caused no changes in their cytotoxic capability. Because tumor products have been implicated in the down-regulation of immune responses, we investigated whether pretreatment with supernatants from the tumor cell line DA-3, derived from the in vivo mammary adenocarcinoma D1-DMBA-3, affects the cytolytic capacity of macrophages. This treatment inhibits, in a dose-dependent fashion, the ability of stimulated normal PEM to kill target cells. Partial purification of DA-3 cell line supernatant showed that most of the inhibitory activity was exerted by factors with a molecular mass greater than 10 kDa and less than 30 kDa. However, slight inhibition could also be observed with fractions containing molecules less than 10 kDa. The data suggest that more than one factor released by the mammary tumor cells may be involved in the down-regulation of macrophage-mediated cytotoxicity. Because the DA-3 cells constitutively produce granulocyte-macrophage CSF (GM-CSF), which has a molecular mass of 27 kDa, we pretreated PEM from normal mice in vitro with rGM-CSF for 24 h. This resulted in a dose-dependent decrease in their capacity to kill tumor target cells upon LPS stimulation. Furthermore, PEM from normal mice injected with rGM-CSF for 25 days displayed a profound decrease in their cytolytic ability against DA-3 targets upon in vitro stimulation with increasing amounts of LPS. The pretreatment of PEM from normal mice with a combination of DA-3 cell supernatants and specific anti-GM-CSF partially neutralized the inhibitory effect of the DA-3 supernatant on macrophage tumoricidal capability. These results indicate that tumor-derived GM-CSF is an important factor involved in the decreased macrophage cytotoxicity during mammary adenocarcinoma progression.
Induction and regulation of casein kinase II during B lymphocyte activation.
Authors: DeBenedette M , Snow E C 
Published: December 2022

Abstract
This study evaluates the regulation of casein kinase II (CK II) activity in resting B cells induced to enter the cell cycle. The induction of B cell cycle progression PMA and ionomycin results in an oscillatory expression of CK II. This kinase activity is also elicited after direct physical interaction between B cells and activated, fixed Th cells, indicating that the increase seen in CK II activity is probably associated with the delivery of the competence-inducing signal to resting B cells. The selective inhibition of ornithine decarboxylase (ODC), the rate-limiting enzyme for polyamine biosynthesis, during PMA and ionomycin-induction of B cell cycle progression, inhibits the expression of CK II activity. The addition of polyamines to cytosolic preparations recovered from cells in which ODC is inhibited results in the appearance of CK II activity, showing that the ODC inhibitor does not directly inhibit the kinase. The treatment of B cells with cycloheximide results in the appearance of CK II activity within 15 min, and this induction is partially explainable by a cycloheximide-elicited increase in cellular levels of polyamines. The artificial elevation of cellular levels of cAMP simultaneous with the addition of PMA and ionomycin results in a 150 to 200% increase in detectable CK II levels, suggesting that the cAMP-dependent signaling cascade may participate during the early regulation of CK II. In contrast, the inhibition of protein kinase C does not adversely influence the early expression of CK II, while actually enhancing kinase activity by 18 h poststimulation.
Macrophages as accessory cells for class I MHC-restricted immune responses.
Authors: Debrick J E , Campbell P A , Staerz U D 
Published: December 2022

Abstract
Ag do not elicit T lymphocyte responses unless they are presented in conjunction with MHC molecules on the surface of an appropriate APC. In the case of CD4+ T lymphocytes dendritic cells can deliver all signals required for complete induction as can macrophages and (activated) B cells. The function of CTL also depends on the presence of specialized accessory cells. Here we show that these accessory cells can behave like scavenger cells. They use foreign Ag in the form of cellular debris as immunogen. They are also crucial for CTL induction because in vivo depletion of phagocytotic cells completely inhibits CTL responses. In these animals CTL activity could be restored by transfer of macrophages. All of the reappearing CTL used MHC restriction elements expressed by the infused macrophages. These experiments suggest that a cognate interaction between macrophages and CTL precursors initiates class I MHC-restricted immune responses.
The role of LFA-1/ICAM-1 interactions during murine T lymphocyte development.
Authors: Fine J S , Kruisbeek A M 
Published: December 2022

Abstract
We have examined the expression and function of the cell adhesion molecules LFA-1 (CD11a/CD18), ICAM-1 (CD54), and ICAM-2 in murine fetal thymic ontogeny and in the adult thymus. On fetal days 14 and 15, 40 to 50% of thymocytes coexpress high levels of LFA-1 and ICAM-1, as determined by flow cytometry. By day 16, more than 90% of fetal thymocytes are LFA-1+ ICAM-1hi, and all IL-2R+ cells are located in this population. Although LFA-1 expression remains unchanged thereafter, ICAM-1 expression appears to be differentially regulated in different thymocyte subpopulations, with CD4+8+ cells being ICAM-1lo and CD4-8- thymocytes remaining ICAM-1hi. ICAM-2 surface expression is dull on both fetal and adult thymocytes. Surprisingly, the expression of ICAM-1 is differentially up-regulated on T cells having a mature phenotype in thymus and in peripheral lymphoid organs, with CD8+ T cells bearing the highest amount of surface ICAM-1. Addition of anti-ICAM-1 or anti-LFA-1 antibodies to fetal thymic organ cultures results in the impaired generation of CD4+8+ cells. These results indicate that LFA-1/ICAM-1 interactions facilitate murine thymic development and suggest that cell adhesion molecules mediate important events in T cell differentiation.
Identification of cell surface receptors for murine macrophage inflammatory protein-1 alpha.
Authors: Oh K O , Zhou Z , Kim K K , Samanta H , Fraser M , Kim Y J , Broxmeyer H E , Kwon B S 
Published: December 2022

Abstract
We have produced recombinant proteins for a cytokine, L2G25BP (macrophage inflammatory protein-1 alpha) (MIP-1 alpha). By using the recombinant protein (rMIP-1 alpha), receptors for MIP-1 alpha were identified on Con A-stimulated and unstimulated CTLL-R8, a T cell line, and LPS-stimulated RAW 264.7, a macrophage cell line. The 125I-rMIP-1 alpha binds to the receptor in a specific and saturable manner. Scatchard analysis indicated a single class of high affinity receptor, with a Kd of approximately 1.5 x 10(-9) M and approximately 1200 binding sites/Con A-stimulated CTLL-R8 cell and a Kd of 0.9 x 10(-9) M and approximately 380 binding sites/RAW 264.7 cell. 125I-rMIP-1 alpha binding was inhibited by unlabeled rMIP-1 alpha in a dose-dependent manner, but not by IL-1 alpha or IL-2. rMIP-1 alpha inhibited the proliferation of unstimulated CTLL-R8 cells. Rabbit anti-rMIP-1 alpha antibodies blocked the growth-inhibitory effect of the rMIP-1 alpha on CTLL-R8 cells.
IL-4-dependent IgE switch in membrane IgA-positive human B cells.
Authors: Zhang X H , Werner-Favre C , Tang H Y , Brouwers N , Bonnefoy J Y , Zubler R H 
Published: December 2022

Abstract
IgE responses by human B cells, separated according to membrane Ig classes, were analyzed in a clonal assay using EL-4 thymoma cells as helper cells, T cell supernatant, and rIL-4. In cultures seeded by means of the autoclone apparatus of the FACS, IgE responses were generated frequently by either IgM (mu+/gamma-alpha-) or IgA (alpha +/mu-)-positive B cells (16 and 14% of the Ig producing wells, respectively), but rarely by IgG (gamma +/mu-)-positive B cells (1.3% of Ig producing wells). The total amounts of Ig secreted by IgM-, IgG-, or IgA-positive cells and the total proportions of responding autoclone wells (23-27%) were comparable. All IgE secretion was IL-4 dependent. When the Ig secretion patterns from alpha +/mu- vs alpha +/mu-epsilon- B cells were compared, most autoclone wells from both types of cells produced IgA only, and similar proportions of IgA producing wells (6.2 and 6.0%) also secreted IgE. In addition, IgE restricted responses occurred 6 times more frequently with alpha +/mu- than with alpha +/mu-epsilon- cells, which suggests that membrane IgA+E double-positive, IgE committed B cells occur in vivo. The isotype pattern generated by alpha +/mu-epsilon- B cells cannot be explained by a chance assortment of separate IgA and IgE precursors or by cytophilic antibody. Thus, IL-4 dependent switch to IgE occurred frequently in IgM- or IgA-positive, but rarely among total IgG-positive, B cells. This could be relevant to IgE production in mucosal tissues rich in IgA expressing B cells.
Contribution of the repeating domains of membrane cofactor protein (CD46) of the complement system to ligand binding and cofactor activity.
Authors: Adams E M , Brown M C , Nunge M , Krych M , Atkinson J P 
Published: December 2022

Abstract
Membrane cofactor protein (MCP) (CD46) of the C system binds to C3b and C4b, functions as a cofactor for their cleavage, and protects autologous cells from C-mediated injury. The predominant structural motif of MCP is the short consensus repeat (SCR), a repeating domain involved in ligand binding of other related C regulatory proteins. SCR deletion mutants were constructed to determine which of the four SCR of MCP contribute to ligand binding and cofactor activity. ELISA were developed to evaluate binding efficiency of mutants to ligand. Analysis of the deletion mutants indicated that the third and fourth SCR were important for both ligand binding and cofactor activity of C3b (iC3) and C4b. In addition, the same SCR were required for efficient binding of an mAb known to inhibit MCP function. The mutant deleted of SCR-2 bound but lacked cofactor activity for iC3. It did not bind or possess cofactor activity for C4b. Deletion of the first (amino-terminal) SCR had a minimal effect on iC3 binding and cofactor activity but reduced the efficiency of C4b binding. The results identify the SCR of MCP that contribute to ligand binding and cofactor activity. The data also suggest the presence of distinguishable iC3 and C4b binding sites and provide evidence that iC3 binding is not always sufficient for cofactor activity.
Molecular heterogeneity of e antigen polypeptides in sera from carriers of hepatitis B virus.
Authors: Takahashi K , Kishimoto S , Ohori K , Yoshizawa H , Machida A , Ohnuma H , Tsuda F , Munekata E , Miyakawa Y , Mayumi M 
Published: December 2022

Abstract
Hepatitis B e Ag (HBeAg) was isolated from pooled sera of carriers, without abnormalities in liver function, by affinity column chromatography with mAb against HBeAg. HBeAg polypeptide with an estimated molecular size of 20,000 Da (p20e) was detected, in addition to regular HBeAg polypeptides (p17e/p18e). p20e, as well as p17e/p18e, did not bind with mAb against the carboxyl-terminal domain of the C-gene product. p20e disclosed an N-terminal sequence of MQLFHLXLII- (X unknown), whereas p17e had that of SKLXLGXLXGMDIDPXKEFG- (X's unknown). By comparing them with the amino acid sequence encoded by the precore region and C gene of hepatitis B virus DNA, p20e was deduced to possess amino acids 1 to 19 of the precore-region product at the N-terminus, which contains signal sequence and usually removed before the secretion of HBeAg. p17e had amino acids 20 to 29 of the precore-region product that continued to the C-gene product. Inasmuch as p20e was invariably detected in HBeAg preparations from carriers without evidence for liver disease, it would not have been released into the circulation from destructed hepatocytes. HBeAg polypeptide bearing an uncleaved signal sequence would help in further understanding the mechanism of HBeAg secretion.
cDNA cloning of mouse NKR-P1 and genetic linkage with LY-49. Identification of a natural killer cell gene complex on mouse chromosome 6.
Authors: Yokoyama W M , Ryan J C , Hunter J J , Smith H R , Stark M , Seaman W E 
Published: December 2022

Abstract
NK cells lyse tumor cells and virally infected cells, but the molecular basis for this phenomenon has not been defined. A mAb specific for the rat cell surface molecule, NKR-P1, stimulates rat NK cell lytic activity and is reactive with all rat NK cells, suggesting that this molecule may play a significant role in NK cell function. We have previously described another NK cell-specific Ag, Ly-49, that belongs to a family of cross-hybridizing genes on distal mouse chromosome 6. The rat NKR-P1 Ag shares several features with the mouse Ly-49 Ag, including selective cell surface expression on NK cells, homology to the C-type lectins, expression as a type II integral membrane protein, and disulfide-linked homodimeric structure. To further examine the relationship of NKR-P1 to Ly-49, we have cloned the cDNA encoding a mouse homologue of NKR-P1 (mNKR-P1). The mouse and rat NKR-P1-deduced polypeptide sequences are highly conserved, suggesting a similar tertiary structure. By examination of DNA from informative recombinant inbred mice with Southern blot analysis, we have determined that mNKR-P1 is encoded by a distinct gene that is genetically linked to the Ly-49 locus, lying within 0.5 centi-Morgan (cM) of Ly-49. Although the deduced amino acid sequences of mNKR-P1 and Ly-49 reveal that these proteins are structurally similar, they are only 24% identical at the amino acid level and the cDNA sequences do not demonstrate significant nucleotide homology. Our studies suggest that we have identified a region on mouse chromosome 6 that includes distinct NK-specific genes that encode structurally related proteins (type II integral membrane proteins, C-type lectin super-gene family) but which demonstrate considerable heterogeneity. We have termed this genetic region the NK complex.
MHC class I-restricted presentation of exogenous antigen by thymic antigen-presenting cells in vitro and in vivo.
Authors: Grant E P , Rock K L 
Published: December 2022

Abstract
We have used a T-T hybridoma, RF33.70, to detect the MHC class I-restricted presentation of exogenous native OVA by thymic APC in vitro. Presentation of OVA with class I molecules by thymic APC requires intracellular processing. Phenotypic analyses indicated that low bouyant density, MHC class II+, FcR+ cells are capable of using this presentation pathway. In order to determine whether thymic APC have this function in vivo, thymic APC were isolated from mice after i.v. injection of native OVA. We find that OVA is presented in association with MHC class I, but not class II, molecules in the thymus. This is in contrast to splenic APC, which present exogenous OVA with both class I and class II molecules under these conditions. Our findings have implications for the repertoire of self-peptides that might be presented by thymic APC to developing T lymphocytes.
Yersinia enterocolitica produces superantigenic activity.
Authors: Stuart P M , Woodward J G 
Published: December 2022

Abstract
We have recently observed that antigenic preparations from Yersinia enterocolitica are capable of inducing strong proliferative responses in normal murine spleen cell cultures. As a consequence of this observation, we evaluated whether Yersinia-derived Ag possess superantigenic activity. Stimulatory activity can be found in culture supernatants, as well as membrane and cytoplasmic fractions of Y. enterocolitica. Cell depletion studies indicate that the primary responding cell is a CD4+ T cell, which requires the presence of APC for responsiveness to Y. enterocolitica Ag. Furthermore, these APC must express MHC class II Ag, as evidenced by the fact that either antibody depletion of class II+ APC or addition of anti-class II antibodies (that block class II Ag on the surface of APC) eliminates the proliferative response. Evaluation of TCR usage by BALB/c T cells responsive to Y. enterocolitica revealed that those T cells bearing V beta 3, 6, and 11 and possibly 7 and 9 were expanded after exposure to Y. enterocolitica Ag preparations. By using a panel of T cell hybridomas, we have shown that hybridomas bearing V beta 3, 7, 8.1, 9, and 11 but not 2, 8.2, 8.3, and 13 respond to Yersinia. When cytoplasmic fractions of Y. enterocolitica were subjected to column chromatography, proliferative activity was enriched approximately 27-fold, and the elution characteristics of the active material suggest that it possesses hydrophobic regions and is, therefore, probably membrane associated. These data indicate that Y. enterocolitica produces antigenic material that has properties consistent with those of T cell superantigens.
Secretion of IL-1: role of protein kinase C.
Authors: Bakouche O , Moreau J L , Lachman L B 
Published: December 2022

Abstract
In an attempt to define the mechanism by which endotoxin induces its biologic activity, LPS was incorporated into phospholipid vesicles (liposomes) and compared with free LPS for ability to stimulate human monocytes. Activation of human monocytes by free LPS caused the translocation of protein kinase C (PKC) from the cytosol to the plasma membranes, the production of both IL-1, alpha and beta, and IL-1 secretion. Activation by LPS presented in multilamellar vesicles (MLV)-LPS caused IL-1 production but not IL-1 secretion. Moreover, MLV-LPS did not induce PKC translocation. MLV themselves did not inhibit monocyte stimulation by LPS, since LPS presented at the surface of lyophilized liposomes behaved like free LPS in cell activation. In contrast, MLV-LPS primed monocytes for subsequent LPS stimulation. When monocytes were activated by LPS in the presence of PKC inhibitors, no plasma membrane-associated PKC or IL-1 secretion was detected, whereas IL-1 production was observed. PKC inhibitors did not affect IL-1 alpha and IL-1 beta production, showing that PKC is not involved in the production of either IL-1. It can be concluded that IL-1 production and secretion are induced independently, and that IL-1 secretion involves PKC.
Mechanisms of IFN-gamma induction by natural killer cell stimulatory factor (NKSF/IL-12). Role of transcription and mRNA stability in the synergistic interaction between NKSF and IL-2.
Authors: Chan S H , Kobayashi M , Santoli D , Perussia B , Trinchieri G 
Published: December 2022

Abstract
We have investigated the molecular mechanisms regulating IFN-gamma production in human T lymphocytes stimulated by NK cell stimulatory factor (NKSF/IL-12). We show that NKSF synergizes with IL-2 and phorbol diesters inducing the accumulation of IFN-gamma mRNA in PHA-activated T cell blasts. NKSF regulates IFN-gamma mRNA expression in PHA blasts and the T leukemia cell line, TALL-103/2, at both the transcriptional and posttranscriptional levels. NKSF increases the transcriptional rate for IFN-gamma in both these cell types, as determined by nuclear run-on analysis. However, synergy between NKSF and IL-2 can be demonstrated only at the level of mRNA stability, and both cytokines are required to increase IFN-gamma mRNA half-life.
Effect of point mutations in the native simian virus 40 tumor antigen, and in synthetic peptides corresponding to the H-2Db-restricted epitopes, on antigen presentation and recognition by cytotoxic T lymphocyte clones.
Authors: Deckhut A M , Tevethia S S 
Published: December 2022

Abstract
The effects on CTL recognition of individual amino acid substitutions within epitopes I, II, and III of SV40 tumor Ag (T Ag) were examined. Epitope I spans amino acids 207 to 215, and epitope II/III is within residues 223 to 231 of SV40 T Ag. An amino acid substitution at position 207 (Ala----Val) or 214 (Lys----Glu) of SV40 T Ag expressed in transformed cells resulted in loss of epitope I, recognized by CTL clone Y-1. The amino acid substitution at residue 214 in the corresponding synthetic peptide, LT207-215(214-Lys----Glu), also led to loss of recognition by CTL clone Y-1. The recognition, by CTL clone Y-1, of peptides LT207-215 and LT207-217 with an Ala----Val substitution at position 207 was severely affected. Peptides LT205-215 and LT205-219 with the Ala----Val substitution at residue 207 were, however, recognized by CTL clone Y-1, suggesting that residues 205 and 206 may be involved in presentation of site I. Alteration of residue 224 (Lys----Glu) in the native T Ag resulted in loss of recognition by both CTL clones Y-2 and Y-3. However, a peptide corresponding to epitope II/III with an identical amino acid substitution at residue 224 provided a target for CTL clone Y-3 but not clone Y-2. A change of Lys----Gln at residue 224 in both the native protein and a synthetic peptide caused loss of recognition by CTL clone Y-2 but not CTL clone Y-3. Further, an amino acid substitution of Lys----Arg at position 224 of the native T Ag decreased recognition of epitope II/III by CTL clones Y-2 and Y-3 but had no effect on recognition of a synthetic peptide bearing the same substitution. These results indicate that the mutagenesis approach, resulting in identical amino acid substitutions in the native protein and in the synthetic peptides, may provide insight into the role of individual residues in the processing, presentation, and recognition of CTL recognition epitopes.
Destructive arthritis without lymphocyte infiltration in H2-c-fos transgenic mice.
Authors: Shiozawa S , Tanaka Y , Fujita T , Tokuhisa T 
Published: December 2022

Abstract
H2-c-fos transgenic (c-fos+) mice are characterized by the inability to raise specific IgG antibodies against immunizing Ag. To examine the contribution of Ag-specific IgG antibody to the development of arthritis, Ag-induced arthritis was produced in c-fos+ mice and their control littermates (c-fos- mice). Intra-articular injection of OVA into c-fos- mice hyperimmunized with OVA induced destructive arthritis with massive lymphocyte infiltration. The c-fos+ mice also developed destructive arthritis comparable in degree with that seen in c-fos- mice. However, joints from the c-fos+ mice had few or no infiltrating lymphocytes. The majority of cells invading the extensively eroded collagenous tissue in the c-fos+ mice had a mesenchymal appearance. These cells, producing excess amounts of c-Fos protein, adhered to and invaded the cartilage matrix when cultured on cartilage slices. These cells, thus, appear to directly cause joint destruction in c-fos+ mice.