bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of IL-6, IL-1, and CD28 signaling in responses of mouse CD4+ T cells to immobilized anti-TCR monoclonal antibody.
Authors: Holsti M A , McArthur J , Allison J P , Raulet D H 
Published: December 2022

Abstract
Purified CD4+ T cells require TCR engagement and Ag-nonspecific co-stimulatory signals to produce IL-2 and proliferate. A number of recent studies have demonstrated that the interaction of the B7 molecule expressed on APC with the T cell-associated CD28 molecule provides a potent co-stimulatory signal to both freshly isolated CD4+ T cells and cloned Th1 cells. Earlier reports have described the role of cytokines, in particular IL-6 and IL-1, as costimulatory molecules for T cell activation. We previously reported that IL-6 and IL-1 synergize to co-stimulate proliferation of purified mouse CD4+ T cells in conjunction with anti-TCR mAb. In this report we explore the interaction of IL-6, IL-1, and CD28 signaling in the activation of mouse CD4+ T cells, and demonstrate that the co-stimulatory requirements of the cells vary depending on the mode of TCR stimulation. CD28 signaling is not sufficient to co-stimulate responses of high buoyant density CD4+ T cells to anti-TCR-conjugated agarose beads; there is an additional requirement that can be supplied by exogenous IL-6 but not by IL-1. In contrast, in responses to anti-TCR mAb that is passively bound to the bottom of culture wells, CD28 stimulation is sufficient to co-stimulate proliferation, resulting in a very high level of IL-2 production; there is no additional requirement for exogenous IL-6 or IL-1. Possible explanations for the differential requirement for IL-6 in the two systems are discussed. Our results are consistent with the notion that CD28 signaling plays a central role in co-stimulating T cell responses. However, the results also suggest that, depending on the nature of the TCR stimulus, T cell activation may also require additional co-stimulatory signals provided by cytokines.
Role of DNA fragmentation in T cell activation-induced apoptosis in vitro and in vivo.
Authors: Mogil R J , Shi Y , Bissonnette R P , Bromley P , Yamaguchi I , Green D R 
Published: December 2022

Abstract
Apoptotic cell death, characterized by DNA fragmentation and morphologic changes, has previously been shown to occur in immature thymocytes and some T cell hybridomas after activation. Like some other forms of apoptosis, DNA fragmentation during activation-induced cell death precedes the morphologic events. For apoptosis to proceed, activation of the cells must persist at least to the time of DNA fragmentation, before which the cells can remain viable if the activation signal is removed. Aurintricarboxylic acid (ATA) blocks activation-induced apoptotic cell death in a T cell hybridoma, and kinetic studies show that this inhibition occurs at or near the time of DNA fragmentation in the cells. Taken together with the ability of ATA to inhibit DNA fragmentation in isolated nuclei exposed to Ca2+ and Mg2+, these data strongly suggest that ATA prevents apoptosis via its ability to inhibit endogenous endonuclease activity, and, conversely, that this activity is required for this form of cell death. In vivo, ATA inhibits thymocyte depletion and DNA fragmentation induced by anti-CD3 Ab. Further, specific loss of V beta 8+ thymocytes after administration of staphylococcal enterotoxin B is blocked by administration of ATA. These observations support an essential role for DNA fragmentation as an irreversible step in activation-induced apoptosis in T cell hybridomas and during T cell development. This is contrasted with heat shock-induced cell death, in which inhibition of DNA fragmentation does not prevent loss of cell viability.
In vitro adhesive interactions between rat lymphocytes and lacrimal gland acinar epithelium. Phenotype of adherent lymphocytes and involvement of adhesion molecules.
Authors: O'Sullivan N L , Skandera C A , Chin Y H , Montgomery P C 
Published: December 2022

Abstract
The selective interaction of trafficking lymphocytes with glandular epithelial cells is thought to link the lacrimal gland (LG) to the mucosal immune network. An in vitro binding assay was used to determine the phenotype of adherent cell populations and to study the involvement of lymphocyte adhesion molecules in the adherence process. Enriched B cell populations showed greater binding to LG epithelium than did enriched T cell populations. Direct phenotyping of adherent lymphocytes demonstrated that B lymphocytes (particularly IgA+ and IgG+ cells) were the predominant participants in LG binding. In vitro binding to LG acinar epithelium was inhibited by mAb with specificity for rat lymph node and Peyer's patch homing receptors and, to a lesser degree, by anti-VLA-4 and LFA-1 but not by anti-CD44 or Thy-1. In addition, the presence of rat lymph node and Peyer's patch homing receptors on endogenous LG lymphocytes was demonstrated by flow cytometry. These data show that B cells are the predominant population adhering to LG epithelium and suggest that lymphocyte homing receptors mediate the adherence process. These findings indicate that selective interactions between lymphocytes and the glandular epithelium contribute to the presence of IgA-producing cells in the LG.
Characterization of the human CD27 ligand, a novel member of the TNF gene family.
Authors: Hintzen R Q , Lens S M , Beckmann M P , Goodwin R G , Lynch D , van Lier R A 
Published: December 2022

Abstract
CD27 is a lymphocyte-specific member of the TNF/NGF-R family that is highly induced on T cells after TCR stimulation, primarily on lymphocytes belonging to the unprimed CD45RA+ subset. However, after prolonged activation both in vivo and in vitro, CD27 expression is gradually switched off. In search of physiologic signals that influence CD27 expression, we found that B cell lines can mediate down-regulation of CD27 surface expression on activated T cells via direct cell-to-cell contact and that preincubation of activated T cells with CD27 mAbs prevented this modulation. Based on these observations, we hypothesized that a ligand for CD27L is expressed on B cell lines and that ligand interaction would result in down-modulation of the molecule from the T cell surface. To identify this putative CD27L, mAbs were raised against the Burkitt cell line Ramos and screened for their ability to block down-modulation of CD27 on activated T cells. Using this approach, we isolated a mAb, designated 2F2, that inhibits CD27 down-regulation in a dose-dependent manner. We demonstrate that this mAb recognizes CD27L as it 1) reacted to mouse fibroblasts expressing the recently cloned CD27L, a novel surface-expressed member of the TNF gene family, and 2) prevented binding of a soluble CD27-Fc construct to a CD27L expressing cell line. Down-regulation of CD27 from the T cell surface by recombinant CD27L was shown to be at least partially caused by release of soluble CD27. The 2F2 mAb enabled us to begin to analyze the biochemical properties, tissue distribution, and function of the CD27L on human cells. From cell lysates of 125I surface-labeled Burkitt cells a complex immunoprecipitation pattern with dominant bands of 29, 55, and 122 to 127 kDa was obtained using the 2F2 mAb. Phenotypical analyses showed that freshly isolated lymphocytes lacked CD27L expression, but that expression of the molecule could be induced after in vitro stimulation of T and B cells. No expression was found on cells of the myeloid lineage or on endothelial cells. Finally, blocking of naturally expressed CD27L by the 2F2 mAb exerted a potent inhibitory effect on the proliferation of T cells in response to allogeneic B cells and PHA. The data presented in this paper identify CD27 and its ligand as potentially important structures involved in cellular interactions between T and B lymphocytes.
ICAM-1-independent, CD18-dependent adhesion between neutrophils and human airway epithelial cells exposed in vitro to ozone.
Authors: Tosi M F , Hamedani A , Brosovich J , Alpert S E 
Published: December 2022

Abstract
Inhalant exposure to ozone can cause diffuse airway epithelial injury that is associated with an inflammatory response, including the influx of neutrophils into lung and airway tissue. We have previously documented enhanced adhesiveness by neutrophils for human airway epithelial cells in in vitro models of diseases associated with airway inflammation and have suggested that this enhanced adhesion may contribute to neutrophil-mediated airway injury. When primary human tracheal epithelial cell (TEC) monolayers were exposed to ozone at 2.0 ppm for 30 min or 0.5 ppm for 2 h, the percentage of PMN adhering to these cells increased from &lt; 5% to a maximum of approximately 75% by 18 to 24 h after the ozone exposure. No change was observed within the first 2 h after ozone exposure, but there was a statistically significant increase in PMN adhesion by 8 h after exposure. In contrast to previous studies with cytokine exposure or respiratory virus infection of TEC, the increased adhesion after ozone exposure was not associated with an increase in epithelial expression of ICAM-1. Consistent with the lack of induction of ICAM-1 by ozone exposure was the observation that anti-ICAM-1 mAbs (mAb; R6.5) previously shown to block PMN adhesion to TEC with increased ICAM-1 expression had no effect on PMN adhesion to ozone-exposed TEC. However, mAbs against CD11b or CD18 on PMN blocked PMN adhesion to ozone-exposed TEC by approximately 55 and 80%, respectively. Chemoattractant preactivation of PMN (e.g., with 10 nM FMLP) was necessary to achieve the highest levels of adhesion to ozone-treated TEC, in marked contrast to our earlier studies with PMN adhesion to cytokine-treated or virus-infected TEC in which resting and prestimulated PMN exhibited the same high levels of adhesion. We conclude that exposure of human TEC in vitro to ozone results in markedly increased adhesiveness for neutrophils that is caused by the induction of as yet uncharacterized epithelial cell adhesion molecules other than ICAM-1 that function as counterreceptors for the CD11/CD18 integrins on PMN. Maximal PMN adhesiveness to ozone-exposed TEC in this system requires preactivation of the PMN, e.g., with FMLP, suggesting important differences in the way PMN interact with ozone-treated vs cytokine-treated or virus-infected TEC.
Chronic graft versus host disease-associated autoimmune manifestations are independently regulated by different MHC class II loci.
Authors: Bradley D S , Jennette J C , Cohen P L , Eisenberg R A 
Published: December 2022

Abstract
Murine chronic graft vs host disease (GVHD) resembles human SLE in autoantibody specificities and glomerulonephritis. Chronic GVHD is induced by donor T cell recognition of recipient Ia Ag. This study compared the role of the two murine class II loci by inducing GVHD in donor/recipient combinations differing at the I-A, I-E, or both I-A and I-E loci. Serum autoantibody levels were mostly higher in I-E-induced GVHD, compared with I-A GVHD, and anti-Sm and anti-dsDNA were produced only in the I-E groups. When the GVHD was induced by differences at both I-A and I-E loci, autoantibody levels and specificities were generally comparable to the I-E group. Only anti-DPP-IV and IgG2bb-specific IgM rheumatoid factor were expressed at higher levels in the I-A and the I-A/E groups, but both autoantibodies were also present in the I-E group. Renal disease, in contrast to autoantibody production, was significantly greater in I-A-induced GVHD. Proteinuria was detected in both the I-A and I-A/E groups, but not in the I-E group. Histopathologic data also showed substantial glomerulonephritis in the I-A and I-A/E groups, but little in the I-E group. IgM deposits were detected in the mesangial region of all groups, but were more marked in the I-A and I-A/E groups. IgG deposits were far more prevalent in the I-A and I-A/E groups and were located predominantly in the capillary walls. These results show a direct relationship between the recognition of specific foreign Ia molecules and the autoimmunity observed: I-E resulted in elevated autoantibody production; I-A resulted in glomerulonephritis; whereas both I-A and I-E resulted in additive autoimmune manifestations. These results also showed an apparent disparity between the presence of commonly measured autoantibodies and the development of renal disease. This work provides a model to delineate further the regulatory role of the MHC class II loci in the development of autoimmunity.
Accumulation of multiple T cell clonotypes in lungs of healthy individuals and patients with pulmonary sarcoidosis.
Authors: Dohi M , Yamamoto K , Masuko K , Ikeda Y , Matsuzaki G , Sugiyama H , Suko M , Okudaira H , Mizushima Y , Nishioka K 
Published: December 2022

Abstract
T cell accumulation and activation in lung may play a major role in the pathogenesis of immunologic lung diseases such as sarcoidosis. Using the combination of RT-PCR and subsequent single-strand conformation polymorphism analysis, we examined T cell clonality in lung and peripheral blood of healthy individuals (n = 5) and patients with active pulmonary sarcoidosis (n = 7). RNA was extracted from PBLs and bronchoalveolar lavage fluid cells, and converted to cDNA. PCR was performed using a set of V beta-C beta primers (V beta 1-20). Products were denatured and electrophoresed in nondenaturing 5% polyacrylamide gel. The existence of a distinct T cell clonotype was detected as a band on a smear. In both groups T cells in PBLs showed a number of clones that expanded. A significantly greater number of clones was detected in BAL compared with PBL in both groups (normal: 25.3 +/- 7.2 in PBL vs 62.8 +/- 5.2 in lung; sarcoid: 25.0 +/- 6.2 in PBL vs 90.0 +/- 6.6 in lung, mean value +/- SEM). In sarcoid lung greater numbers of clones were detected than in lungs of healthy controls (p &lt; 0.012). These clonal expansions were observed over all the 20 V beta families examined, and were not restricted to certain V beta families. These results suggest that there are clonal expansions even in normal lung, and that in sarcoidosis, apparently, additional T cell clones using multiple V beta segments might be activated and accumulated at the site of the disease.
Fc gamma RII cross-linking inhibits anti-Ig-induced erg-1 and erg-2 expression in BCL1.
Authors: Gottschalk A R , Joseph L J , Quintáns J 
Published: December 2022

Abstract
Activation of B cells through their Ag receptor is known to be negatively regulated by Fc gamma RII engagement. To explore the molecular and biochemical mechanisms of Fc gamma RII-mediated inhibition, we investigated the effect of Fc gamma RII engagement on the expression of two immediate-early genes, egr-1 and egr-2, and tyrosine phosphorylation events following the activation of the murine B cell line, BCL1. Egr-1 and egr-2 were expressed in BCL1 after slg cross-linking. The induction of egr-1 and egr-2 expression was prevented when the Fc gamma RII was co-cross-linked with slg in BCL1, but not in WEHI-231. The inhibitory effects of Fc gamma RII engagement on egr-1 and egr-2 expression occurred when the Fc gamma RII was cross-linked with either slgM or slgD. Treatment with cyclosporin A prevented the expression of egr-2 induced by slg cross-linking, but did not inhibit egr-1 expression. In addition, cyclosporin A did not prevent the negative-regulatory effects of Fc gamma RII engagement on egr-1 expression, suggesting that the Fc gamma RII works upstream from the site of action of cyclosporin A. To investigate activation signals more proximal to the plasma membrane, we compared tyrosine phosphorylation patterns of several effector molecules known to play a role in B cell activation. Cross-linking of slg induced tyrosine phosphorylation of the p62 GAP-associated protein. The p62 protein became hyperphosphorylated in response to co-cross-linking of slg with Fc gamma RII. Our results identify egr-1 and egr-2 as targets of Fc gamma RII-mediated inhibition of anti-Ig-induced B cell activation. In addition, they show that negative regulation by Fc gamma RII is effective in both cyclosporin A-sensitive and insensitive pathways. Further, we suggest a possible Fc gamma RII signaling pathway leading to the inhibition of egr-1 and egr-2 expression.
Tyrosine phosphorylation and activation of Vav GTP/GDP exchange activity in antigen receptor-triggered B cells.
Authors: Gulbins E , Langlet C , Baier G , Bonnefoy-Berard N , Herbert E , Altman A , Coggeshall K M 
Published: December 2022

Abstract
Ag receptor triggering in B cells stimulates the activity of receptor-associated tyrosine protein kinases (TPK), leading to tyrosine phosphorylation of several cellular substrates, one of which is the Vav proto-oncogene product. We have recently determined that Vav is a TPK-regulated guanine nucleotide exchange factor for Ras in T cells. Here, we show that B cell extracts or Vav immunoprecipitates contain a Ras GDP/GTP exchange activity that is stimulated upon surface Ig (slg) triggering. The receptor-mediated stimulation of Vav exchange activity was blocked by the TPK antagonist, herbimycin A. Furthermore, immunodepletion of Vav from the B cell extracts removed approximately 80% of the Ras GDP/GTP exchange activity. These findings indicate, first, that B cell-derived Vav possesses GDP/GTP exchange activity for Ras; second, that the exchange activity of Vav is accelerated by a slg-triggered, herbimycin A-sensitive TPK and, third, that Vav accounts for most of the receptor-stimulated Ras GDP/GTP exchange activity. Thus, Vav may serve as a critical component in slg-mediated signal transduction pathways by coupling receptor-associated TPK to the activation of Ras proteins.
Regulation of CD23 expression by IL-4 and corticosteroid in human B lymphocytes. Altered response after EBV infection.
Authors: Paterson R L , Or R , Domenico J M , Delespesse G , Gelfand E W 
Published: December 2022

Abstract
Cellular CD23 has been implicated in various biologic and pathologic processes. Here, we have studied the regulation of B cell CD23 expression and function by the synthetic corticosteroid, dexamethasone (DEX). We report that DEX acts directly on B lymphocytes to down-regulate IL-4-induced CD23 expression, whereas in parallel the IL-4R is up-regulated. Down-regulation of CD23 occurred at the cell surface and for shed material in culture medium. EBV infection of B cells is linked to development of lymphoproliferative diseases, including lymphoma, and there is evidence that EBV-stimulated CD23 expression may be instrumental in the inappropriate survival of infected cells. We have determined that treatment of EBV-infected cells with IL-4 leads to a synergistic up-regulation of B cell CD23. Furthermore, infection of B cells by EBV introduced a relative resistance to the down-regulatory effects of DEX on IL-4-induced CD23 expression.
CD40 ligand acts as a costimulatory signal for neonatal thymic gamma delta T cells.
Authors: Ramsdell F , Seaman M S , Clifford K N , Fanslow W C 
Published: December 2022

Abstract
The stimulatory requirements for T cells bearing gamma delta T cell receptors are distinct from those of alpha beta T cells. We have analyzed the ability of the CD40 ligand (CD40L) to activate neonatal thymic gamma delta T cells. CD40L is expressed on activated T cells and has been shown to induce B cell proliferation and Ig secretion as well as monocyte activation. We now demonstrate that, in the presence of an anti-TCR-gamma delta Ab, CD40L is able to induce the proliferation of neonatal thymic gamma delta cells. The presence of CD40L also leads to enhanced expression of a variety of activation-associated Ag including CD25, CD69, CD44, and Ly6C. In addition to proliferation, CD40L induces lectin-mediated cytolytic activity in thymic gamma delta T cells as well as the production of IFN-gamma and TNF-alpha. We were unable to detect IL-2 or IL-4 production in response to CD40L, and Ab-blocking studies indicate that the mechanism of activation appears to involve IL-1 but is independent of IL-2, IL-4, and IL-7. These results suggest that, in addition to its effects on B cells and monocytes, CD40L can costimulate the activation of thymic gamma delta T cells.
Characterization of influenza A virus binding sites on human neutrophils.
Authors: Rothwell S W , Wright D G 
Published: December 2022

Abstract
Exposure of human neutrophils (PMN) to influenza A virus (IAV) triggers discrete responses in these cells that interfere with their normal host defense functions. Because the restricted host range and tissue specificities of many viruses are determined by cell surface molecules acting as virus receptors on target cells, it seemed plausible that IAV might interact with neutrophils via specific plasma membrane glycoproteins that bind to viral hemagglutinin. When the binding of intact IAV (ATCC strain A/PR/8/34 (H1N1)) to PMNs was examined by flow cytometry, virus binding was found to be saturable and to be diminished after extensive desialation of the cells with neuraminidase. Stimulation of PMNs with FMLP (0.1 microM) caused a transient increase in IAV binding that was maximal (&gt; 200%) at 2 min after stimulation. When neutrophil membrane proteins were separated by gel electrophoresis and transferred to nitrocellulose, IAV bound selectively to two polypeptide bands of approximately 125 and 160 kDa. Relative binding to these two bands was modified and ultimately eliminated by treatment of PMN membrane proteins with neuraminidase before electrophoresis and blotting. Intact virus precipitated a limited number of proteins from solubilized PMN plasma membrane preparations, and Abs specific for sialophorin (CD43) recognized virus-precipitated PMN membrane proteins of the same apparent m.w. as those detected in virus-membrane protein blots. These findings indicate that IAV binds to human PMNs through interactions with a limited number of PMN membrane glycoproteins, which include sialophorin (CD43).
Bispecific anti-CD22/anti-CD3-ricin A chain immunotoxin is cytotoxic to Daudi lymphoma cells but not T cells in vitro and shows both A-chain-mediated and LAK-T-mediated killing.
Authors: Shen G L , Li J L , Vitetta E S 
Published: December 2022

Abstract
We have generated a bispecific anti-CD22/anti-CD3 immunotoxin (IT) and determined whether it would exert both lymphokine-activated killer (LAK) T cell-mediated and ricin A chain (dgA)-mediated toxicity to Daudi tumor cells but not to T cells in vitro. One parental IT, Fab'-anti-CD22-dgA makes a potent immunotoxin for B cells, but not T cells, while the other, Fab'-anti-CD3-dgA, kills neither T nor B cells. Three mouse quadromas were generated and the bispecific Abs (BsAbs) were purified by double affinity chromatography. Two of the three purified BsAbs induced significant proliferation and IL-2 production in T cells. All three BsAbs induced LAK-T cell-mediated specific lysis of CD22+ Daudi cells. Two of the purified Ab were conjugated to dgA. Using a 51Cr release assay in the presence of LAK-T cells and Daudi target cells, the IC50s of the BsAbs were 3.5 x 10(-10) M and 9 x 10(-11) M, as compared to 2.1 x 10(-11) M and 3.2 x 10(-11) M, for their respective ITs. Hence, in the presence of LAK-T cells, the BsITs were 3- to 17-fold more cytotoxic than unconjugated BsAbs in 51Cr-release assays. Daudi cells were also treated in vitro with different mixtures of LAK-T cells, BsAbs, and BsITs and then adoptively transferred into SCID mice. As determined by the mean paralysis time of the recipients, in the presence of LAK-T cells the BsITs had impressive anti-tumor activity.