bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevention of lymphadenopathy in MRL-lpr/lpr mice by blocking peripheral lymph node homing with Mel-14 in vivo.
Authors: Mountz J D , Gause W C , Finkelman F D , Steinberg A D 
Published: December 2022

Abstract
MRL-lpr/lpr mice develop massive lymphadenopathy and autoimmunity. There is evidence that both migration and local proliferation contribute to the accumulation of Ly-2-, L3T4-, 6B2+ T cells in the peripheral lymph node (PLN). Mel-14 is an antibody which binds to the lymphocyte lymph node homing receptor (gp90Mel-14) and can block migration of lymphocytes to the PLN. Treatment of mice from birth to 11 wk of age with Mel-14 and another rat IgG2a mAb, 6B2, resulted in reduction (10- to 20-fold) in lymphadenopathy. Mel-14, but not 6B2, preferentially reduced the percentages of Thy-1+, 6B2+ lymphocytes in the lymph node. Treatment with a third antibody, anti-Ly-1, had no effect on lymphadenopathy. Mel-14 treatment resulted in diversion of the Ly-2-, L3T4-, 6B2+, gp90Mel-14 cells to the spleen and consequently induced marked splenomegaly. Thymocytes from MRL-lpr/lpr and MRL-+/+ mice were analyzed by two-color flow cytometry analysis after depletion of Ly-2+ and L3T4+ T cells. There was no difference in the percent of Ly-2-, L3T4-, 6B2+, gp90Mel-14 positive thymocytes comparing these two strains. Mel-14 treatment did not alter Ig levels or autoantibody production. These studies suggest Mel-14 reduced lymphadenopathy by interfering with homing to PLN, whereas 6B2 may have interfered with marrow production of precursor cells or killed 6B2+ cells after they exited the marrow. The data are consistent with the idea that lymphadenopathy occurs in MRL-lpr/lpr mice due to increased homing gp90-Mel-14 T cells to the PLN and that gp90Mel-14 is a necessary receptor for the abnormal 6B2+ T cells.
Neurotensin enhances IL-1 production by activated alveolar macrophages.
Authors: Lemaire I 
Published: December 2022

Abstract
Peptides may play a physiologic role in regulating immune responses and in triggering a variety of cellular events that modify the sensitivity of cells in the periphery. Neurotensin (NT) is present in the lung and it has been shown to bind to mouse peritoneal macrophages and influence their phagocytic ability. In this study, the effect of NT on the production of IL-1 by rat alveolar macrophages (AM) has been investigated. Although NT did not stimulate the release of IL-1 or increase the apparent intracellular pool of IL-1 when incubated with AM, there was significant cell changes, such as increased adherence, spreading, and altered shape. Furthermore, when AM were stimulated with LPS, both the intracellular and extracellular pools of IL-1 were significantly increased by NT. This effect was dose dependent and was observed at concentrations ranging from 10(-11) to 10(-6) M. NT did not modify the kinetics of LPS-induced IL-1 release nor the effects of a given suboptimal concentration of LPS. The release of IL-1 by various inducers, including muramyl dipeptide (MDP) and zymosan was also enhanced by NT, suggesting a general modulator role for this neuropeptide. When NT was added concomitantly with other potentiators of IL-1 production, such as IFN-gamma and leukotriene B4, no synergistic effect on IL-1 release was seen. Kinetics experiments showed that optimal enhancement of IL-1 production occurred when AM cultures were preincubated with NT before addition of MDP or when NT and MDP were present together at the initiation of the 24-h AM cultures. Taken together, our data suggest that NT acts early in the induction process of IL-1. Because IL-1 plays an important role both in the initiation of the immune response and in the local manifestations of inflammation, NT released in the vicinity of pulmonary blood vessels and the respiratory epithelium may modulate immunologically relevant responses in the lung microenvironment.
Tumor necrosis factor-alpha up-regulates expression of secretory component, the epithelial receptor for polymeric Ig.
Authors: Kvale D , Løvhaug D , Sollid L M , Brandtzaeg P 
Published: December 2022

Abstract
Secretory component (SC) is the receptor that facilitates transcytosis of polymeric IgA and polymeric IgM through secretory epithelial cells and into exocrine fluids. The present study showed that rTNF-alpha enhanced the cellular pool, membrane expression, and secretion of functionally SC in a human colonic carcinoma cell line (HT-29m2) which is known to express and process SC like normal glandular cells. TNF-alpha also up-regulated membrane expression of the constitutive HLA class I molecules, whereas the cells remained HLA class II-negative.
Antigenic specificities of human monoclonal and polyclonal IgM rheumatoid factors. The C gamma 2-C gamma 3 interface region contains the major determinants.
Authors: Sasso E H , Barber C V , Nardella F A , Yount W J , Mannik M 
Published: December 2022

Abstract
The binding site specificity of 12 monoclonal and 11 polyclonal IgM rheumatoid factors (RF) isolated from human plasma or serum has been studied. All IgM RF bound best to sites on IgG and intact Fc. The monoclonal IgM RF did not bind at all to fragments lacking the C gamma 2 or C gamma 3 domains. In contrast, low level binding to the pFc' fragment, composed of the C gamma 3 domain, was seen with seven IgM RF, mainly from patients with rheumatoid arthritis (RA). IgG1 binding appeared to be a requisite specificity of all human IgM RF. IgM RF binding to IgG3 subclass was common among the monoclonal IgM RF. Most RA polyclonal IgM RF but only 2 of the monoclonal IgM RF possessed the IgG1, 2 and 4 binding pattern. Monoclonal IgM RF which bound best to histidine-modified IgG also bound well to IgG3. The 7-kDa fragment D of staphylococcal protein A inhibited the IgG binding of most monoclonal and to a lesser degree polyclonal IgM RF. Thus, the results indicate that the C gamma 2-C gamma 3 interface region of IgG contains the predominant determinants for monoclonal and polyclonal IgM RF. For some monoclonal IgM RF the binding site, even though at the interface of the C gamma 2 and C gamma 3 domains, is not the staphylococcal protein A site. Furthermore, polyclonal IgM RF possess specificities not encountered among the monoclonal IgM RF. These specificities may have special
Biochemical characterization of an Fc gamma receptor purified from human neutrophils.
Authors: Fleit H B , Kuhnle M 
Published: December 2022

Abstract
The Fc receptor identified by mAb 3G8 (Fc gamma RIII) was isolated by mAb affinity chromatography from 0.5 to 2 x 10(10) neutrophils yielding 33 to 149 micrograms of protein. Iodination of the purified protein identified a polypeptide of broad electrophoretic mobility from Mr 47 to 70 kDa and occasionally a fainter polypeptide at 100 to 130 kDa, which may be dimerized receptor. Two-dimensional isoelectric focusing gel electrophoresis illustrated multiple diffuse polypeptides ranging from a pI of less than 4.7 to 6.5. Treatment of the purified receptor with neuraminidase shifted the mobility of these polypeptides to a more basic pI, ranging from 6 to 8, illustrating the presence of sialic acid residues on Fc gamma RIII. The glycoprotein nature of Fc gamma RIII was characterized by several criteria. The receptor bound to Con A-Sepharose. Treatment of Fc gamma RIII with endoglycosidase H or F, which cleave high mannose and biantennary complex N-linked oligosaccharides, respectively, failed to alter the electrophoretic mobility of the Fc gamma R. Peptide N:glycosidase F, which cleaves all classes of N-linked oligosaccharides, reduced the Mr of Fc gamma RIII by 60% to reveal two poorly resolved polypeptides centered at Mr 25 kDa and ranging from Mr 16 to 28 kDa. Chemical deglycosylation with trifluoromethanesulfonic acid, which cleaves O- and N-linked oligosaccharides except for the asparagine-linked N-acetylglucosamine, reduced the Mr of Fc gamma RIII to 21 to 36 kDa. These results demonstrate that Fc gamma RIII is an acidic complex sialoglycoprotein and suggest that there may be 8 to 15 N-linked oligosaccharide chains on Fc gamma RIII.
Induction and regulation of CD2 mRNA in human lymphocytes.
Authors: Malter J S , Reed J C , Kamoun M 
Published: December 2022

Abstract
Herein we studied the accumulation and decay of CD2 mRNA in human PBMC stimulated with PHA. The data show that CD2-specific messages are present in low quantities in resting PBMC and are rapidly increased by five- to sevenfold within 24 h of addition of optimal amounts of PHA. Similar induction of CD2 mRNA was seen after stimulation of PBMC with anti-CD3 mAb and PMA. Peak levels of CD2 message were maintained until 72 h post-stimulation and declined gradually thereafter. Despite stimulation with Staphylococcus aureus and PMA, purified B cells failed to demonstrate any CD2 mRNA. Unlike transferrin or IL-2R mRNA, Il-2 had no effect on the accumulation of CD2 messages in resting or PHA-stimulated PBMC. The time course of CD2 mRNA accumulation preceded lymphocyte proliferation and the appearance of additional cell surface CD2 Ag. The decay of CD2 mRNA was very rapid, with a t 1/2 of approximately 45 min. The protein synthesis inhibitor, cycloheximide, increased its half-time by fourfold to 3.5 h. The data imply the existence of a labile factor, dependent on protein synthesis that is important in the regulation of CD2 mRNA. Compared to other PHA-inducible lymphocyte genes, the kinetics of CD2 transcript accumulation are most reminiscent of the oncogenes N-ras and c-abl.
Rabbit MHC. II. Sequence analysis of the R-DP alpha- and beta-genes.
Authors: Sittisombut N , Mordacq J , Knight K L 
Published: December 2022

Abstract
Molecular genetics studies have recently revealed complexity in the MHC class II region that has not been detected by previous serologic and genetic studies. In humans, three subregions, DP, DQ, and DR, of the class II genes as well as the DZ alpha and DO beta genes, have been extensively characterized. Although homologs of these human genes were identified in many species, their expressibility has not been well defined in species other than the mouse. We have previously cloned the rabbit homologs of the HLA-DP alpha and beta genes whose protein products had never been detected. The sequences of rabbit DP alpha 1 and DP beta genes are reported herein and they indicate that the rabbit DP genes encode functional alpha- and beta-chains. Unfavorable nucleotides surrounding the first AUG codon may, however, reduce the translational efficiency of the R-DP beta mRNA and explain the difficulty in generating serologic reagents specific for rabbit DP molecules. A complex mutation in the beta 1 domain of the R-DP beta gene was similar to the one found in the H-2A beta 1 gene of five strains of mice. The origin of this mutation is discussed.
Anti-CD3 and phorbol myristate acetate regulation of MHC unrestricted T cell cytotoxicity. Lack of a requirement for CD3/T cell receptor complex expression during tumor cell lysis.
Authors: Thiele D L , Patel S S , Lipsky P E 
Published: December 2022

Abstract
The effects of anti-CD3 mAb on MHC-unrestricted cytotoxic activity of NK depleted PHA-activated human T cells were examined. Anti-CD3 mAb had variable effects on killing of K562 or Daudi targets. Whereas lower concentrations of OKT3 often inhibited lysis of either target, higher concentrations (greater than 1 micrograms/ml) frequently increased K562 killing and always augmented Daudi lysis. However, lysis of the renal cell carcinoma, Cur, was consistently inhibited by OKT3 over a broad concentration range. Such variable effects were not related to differential regulation of heterogeneous subsets of effector cells, as similar patterns of OKT3-mediated modulation of tumor cell lysis by T cell clones was also observed. Another IgG2a anti-CD3 mAb, 64.1, and either F(ab')2 fragments of OKT3 or intact OKT3 in the presence of aggregated human Ig were found to inhibit lysis of Cur, K562, and Daudi targets consistently. Additional experiments were carried out to determine whether modulation of CD3 accounted for the inhibitory effects of the anti-CD3 mAb. PMA was noted to cause modulation of CD3 from the surface of PHA or alloantigen-activated T cells, and the combination of anti-CD3 and PMA caused even more marked modulation of CD3. Whereas preincubation with PMA and/or anti-CD3 decreased alloantigen-specific cytotoxic T cell function in relative proportion to the loss of CD3 expression, no consistent relationship between CD3 expression and the capacity of PHA-activated T cells to kill Cur targets was noted. PMA alone caused no consistent alteration of Cur lysis. Moreover, in the presence of PMA, anti-CD3 mAb caused no significant inhibitory effect on Cur lysis, in spite of increased modulation and in some cases virtual total loss of surface CD3 expression. These findings indicate that when FcR interactions are prevented, anti-CD3 mAb consistently inhibit MHC-unrestricted cytotoxicity by PHA-activated T cells. Despite this, the data support the conclusion that CD3/TCR complex interactions with target cells are not required for either target cell recognition or triggering of lysis by MHC-unrestricted cytotoxic T cells.
Target cell lysis by cytotoxic T lymphocytes that lack detectable hemolytic perforin activity.
Authors: Allbritton N L , Nagler-Anderson C , Elliott T J , Verret C R , Eisen H N 
Published: December 2022

Abstract
When mouse target cells are subjected to cytolytic attack by mouse CTL cell lines that have been cultured for many months in high levels of IL-2, and have abundant perforin-rich secretory granules, they exhibit two prominent changes: 1) rapid and massive increase (greater than 10-fold) in intracellular Ca2+ concentration and 2) fragmentation of DNA into nucleosome-sized fragments. We show here that when the same target cells are subjected to cytolytic attack by perforin-deficient CTL, either human CTL or primary mouse CTL from peritoneal exudates, the same changes are observed, suggesting that perforin-rich and perforin-deficient CTL kill their target cells by similar (if not identical) mechanisms. It is possible that perforin-deficient CTL produce enough perforin to destroy target cells but not enough to be detected by currently available methods.
IL-4 induces loss of B lymphocyte Fc gamma R II ligand binding capacity.
Authors: Laszlo G , Dickler H B 
Published: December 2022

Abstract
Murine B lymphocytes cultured for 24 h with rIL-4 lost (mean reduction of 88%, range 81 to 96%) the capacity to bind Ag-IgG antibody complexes to B lymphocytes as assessed by flow microfluorometry. This effect was specific in that it was not seen with IL-1, IL-2, or IFN-gamma; IL-4 did not have a similar effect on other B lymphocyte membrane molecules; and the effect was completely prevented by anti-IL-4 (mAb 11B11). More than 60% inhibition of the binding of complexes was seen with as little as 1 U/ml of IL-4 although maximal inhibition was seen with greater than or equal to 30 U/ml. IL-4-induced inhibition of the binding of complexes was time dependent (the effect was first seen after 8 h and was not maximal until 24 h), temperature dependent (it did not occur at 4 degrees C), and reversible (B lymphocytes that had lost the ability to bind complexes due to IL-4 regained this capacity when re-cultured for 24 h in the absence of IL-4). The effect could be partially prevented by IFN-gamma. The inability to bind complexes appeared to be mainly due to an alteration of Fc gamma R (Fc Receptors) II rather than down-regulation of receptor expression because IL-4 induced only a moderate reduction in the binding of two Fc gamma R II specific mAb (20% for 2.4G2 and 32% for K9.361). The IL-4-induced loss of binding of complexes to B lymphocyte Fc gamma R II appears to be a novel form of receptor regulation (function rather than expression), and likely plays a role in the up-regulation of B lymphocytes by IL-4 by preventing Fc gamma R II-mediated inhibition of B lymphocyte responses.
Limiting dilution analysis of TNF producing cells in C3H/HeJ mice.
Authors: Lattime E C , Stoppacciaro A , Stutman O 
Published: December 2022

Abstract
A limiting dilution assay (LDA) that measures the frequency of TNF producing cells is described. LDA determination is based on the inhibition of growth of a highly TNF sensitive subline from the WEHI-164 fibrosarcoma by using a micro assay sensitive to single picogram amounts of recombinant murine TNF. Using such LDA, it was determined that the reported deficiency in LPS-induced TNF production in C3H/HeJ mice is a function of reduced frequency of TNF producing cells rather than a complete lack of responsiveness. In bulk culture, LPS-triggered TNF was produced by Thy-1.2 negative spleen cells with activity recovered in both G10 Sephadex adherent and nonadherent subpopulations. LPS stimulation of spleen cells from C3H/HeJ mice resulted in TNF mRNA expression as shown in both Northern blots and in situ hybridization. The frequency of TNF mRNA bearing cells in control of C3H/HeSnJ mice by in situ hybridization correlated with that found for TNF producing cells in LDA. In C3H/HeJ spleen, significantly higher numbers of TNF mRNA positive cells were found than were shown to produce TNF in LDA.
Lymphokine-independent induction of macrophage membrane IL-1 by autoreactive T cells recognizing either class I or class II MHC determinants.
Authors: Wasik M A , Donnelly R P , Beller D I 
Published: December 2022

Abstract
Here we report that autoreactive T cell clones and T cell hybridomas that recognize class I or class II MHC determinants can induce IL-1 expression on cultured macrophages in an MHC-restricted manner. This genetic restriction of membrane IL-1 (mIL-1) induction is not absolute, however; it is manifest only in macrophages that have been cultured for several days before stimulation. Macrophages that are evaluated within 24 h after adherence display a basal level of mIL-1, and the T cell-induced augmentation of basal mIL-1 expression is not MHC-restricted. It appears that T cells of both Th1 and Th2 type have the capacity to induce mIL-1, suggesting that this function is not limited to the T cell subset (Th2) that is able to use IL-1. Most importantly, the ability of T cells to induce IL-1 on macrophages seems to occur by virtue of direct cellular interactions, and is independent of lymphokine secretion. The induction event is rapid enough (2 to 4 h) to allow T cells to interact with both antigen and IL-1 during the initial T cell/macrophage contact. These findings thus reveal an efficient mechanism for the induction of IL-1 during Ag presentation to T cells.
Characterization of granzymes A and B isolated from granules of cloned human cytotoxic T lymphocytes.
Authors: Krähenbühl O , Rey C , Jenne D , Lanzavecchia A , Groscurth P , Carrel S , Tschopp J 
Published: December 2022

Abstract
A human CD8+ CTL clone with cytolytic potential was shown to express two serine proteases, a 50-kDa homodimer and a 27-kDa monomer, which were purified from cytoplasmic granules. N-terminal sequencing of the purified proteins revealed that the 50-kDa homodimer is the gene product of the human Hanukah factor cDNA clone and that it represents the human homologue to granzyme A. Similarly, the 27-kDa protein was shown to be the serine esterase encoded by the human lymphocyte protease cDNA clone and corresponds to granzyme B. There was no evidence for the presence of other granzymes, in particular for the human homologues to murine granzymes C, D, E, and F. The substrate best cleaved by granzyme A was Gly-Pro-Arg-amido-4-methyl-coumarin after the Arg residue and the pH optimum was 8 to 8.5. Upon triggering of the TCR-CD3 complex with an anti-CD3 mAb, granzyme A was released into the culture medium. Furthermore, a granule-associated hemolytic activity was detected after salt extraction and partial purification of granule proteins. This suggests that hemolytically active human perforin can be obtained from inactive granules.
Study of the epitope structure of purified Dac G I and Lol p I, the major allergens of Dactylis glomerata and Lolium perenne pollens, using monoclonal antibodies.
Authors: Mourad W , Mécheri S , Peltre G , David B , Hébert J 
Published: December 2022

Abstract
The use of mAb allowed us to further analyze the cross-reactivity between purified Dac g I and Lol p I, the major allergens of Dactylis glomerata (cocksfoot) and Lolium perenne (Rye grass), respectively. It was first shown, using IEF, followed by immunoprinting, that serum IgE antibodies from most grass-sensitive patients recognize both Dac g I and Lol p I. Second, three different anti-Lol p I mAb, 290A-167, 348A-6, and 539A-6, and one anti-Dac g I mAb, P3B2 were all shown to react with Dac g I and Lol p I, indicating that the two molecules share common epitopes. Epitope specificity of the mAb was determined by competitive binding inhibition of a given labeled mAb to solid phase fixed Dac g I or Lol p I by the mAb. The results indicated that the four mAb are directed against four different and non-overlapping epitopes present on both allergens. Using double-binding RIA, our data strongly suggest that the common epitopes are not repetitive on both molecules. In addition to their similar physicochemical characteristics, such as isolectric points and m.w., Dac g I and Lol p I share four identical epitopes. Binding inhibition of human IgE to Lol p I and Dac g I by the mAb was also assessed. The results indicated that each mAb was able to inhibit such reactions to variable degree but no additive inhibition was observed when two mAb of different specificities were used in combination, suggesting that the human IgE binding site is partially shared by each epitope recognized by the four mAb.
An 80 to 85 kilodalton human phosphoglycoprotein associated with cell activation.
Authors: Omary M B , Kelleher D , Kagnoff M F 
Published: December 2022

Abstract
This report describes the identification and biochemical characterization of a new proliferation- and activation-associated membrane Ag. The M21C5 Ag (Mr 80 to 85 kDa) initially was immunoprecipitated from 125I-cell surface-labeled HT29 human tissue culture colon cancer cells by using a monoclonal antibody (M21C5) prepared from HT-29 immunized BALB/c mice. The M21C5 Ag is a glycoprotein as shown by metabolic labeling with 3H-leucine and 2-[3H]-mannose. It has a broad distribution on most proliferating tissue culture cell lines tested, but is absent from several normal human tissues that were examined. Although not detected on unstimulated PBL, the expression of the M21C5 Ag could be induced by stimulation of PBL with the T cell mitogens PHA or Con A. Two-color fluorescence analysis showed that M21C5 is expressed on both CD4 and CD8 activated T cells. After mitogen stimulation, the expression of the M21C5 Ag was delayed relative to the expression of IL-2 and transferrin receptors. M21C5 glycoprotein was shown to be an integral membrane protein that is phosphorylated primarily on serine residues. Based on its biochemical and tissue distribution properties, M21C5 phosphoglycoprotein appears distinct from other known proliferation and activation-associated molecules.
Substance P, neurokinin A, and neurokinin B induce generation of IL-1-like activity in P388D1 cells. Possible relevance to arthritic disease.
Authors: Kimball E S , Persico F J , Vaught J L 
Published: December 2022

Abstract
Near nanomolar concentrations of substance P induce production of IL-1 or an IL-1-like activity in the mouse macrophage cell line P388D1. Moreover, this could be accomplished with the carboxyl-terminal octapeptide substance P4-11, and could be inhibited with the substance P antagonist [D-Pro2, D-Trp7,9]-substance P. Two other mammalian neurokinins, neurokinin A and neurokinin B, were also found to induce secretion of IL-1-like activity in P388D1 cells. These findings suggest that activation of immune cells by neuromodulators can contribute to the maintenance of the chronic inflammatory state and the immunopathology observed in arthritic disease mediated by IL-1. The results also suggest that one approach to the treatment of rheumatoid arthritis might be to attempt to inhibit the local effects of immuno-modulatory neuropeptides, specifically the neurokinins, in affected joints.