bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ligation of platelet/endothelial cell adhesion molecule 1 (PECAM-1/CD31) on monocytes and neutrophils increases binding capacity of leukocyte CR3 (CD11b/CD18).
Authors: Berman M E , Muller W A 
Published: December 2022

Abstract
Platelet/endothelial cell adhesion molecule 1 (PECAM-1/CD31) is a member of the Ig gene superfamily expressed on the surfaces of monocytes (Mo), neutrophils (PMN), and some T cell subsets, as well as on platelets and the intercellular junctions of endothelial cells. We used mAbs (mAb) against PECAM on Mo and PMN to mimic interaction with natural ligand. Such treatment resulted in the rapid increase of leukocyte beta 2 integrin-mediated adhesive function, as measured in two in vitro assays. Anti-PECAM-treated Mo bound more rapidly and in a CD18-dependent manner to cultured endothelial cells. Monovalent Fab fragments augmented binding significantly and intact IgG, bivalent F(ab')2 fragments, and secondarily cross-linked Fab fragments were even more effective. In a direct assay of CD11b/CD18 (CR3) function, PMN settling on surfaces coated with anti-PECAM mAb (including Fab fragments) were stimulated to bind C3bi-coated erythrocytes. These studies demonstrate that, in addition to the previously described functions of PECAM-1, this molecule is capable of participating in an adhesion cascade resulting in the activation of Mo and PMN beta 2 integrins. This activation may be important for the CR3-dependent adhesion events that are critical in the emigration of Mo and PMN at sites of inflammation.
Inhibition of chemotactic peptide-induced neutrophil adhesion to vascular endothelium by cAMP modulators.
Authors: Derian C K , Santulli R J , Rao P E , Solomon H F , Barrett J A 
Published: December 2022

Abstract
An early event associated with neutrophil-dependent tissue damage involves the adhesion of neutrophils to the vascular endothelium and the subsequent release of oxygen-derived free radicals and granule constituents. Elevations in intracellular cAMP are known to inhibit free radical release but not lysosomal enzyme release. The role of cAMP in FMLP-induced neutrophil adhesion was examined in this study by using an in vitro model of neutrophil-endothelial cell adhesion. FMLP stimulated a time- and concentration-dependent increase in human neutrophil adhesion to HUVEC. FMLP-mediated adhesion was inhibited by a diverse group of cAMP modulators: forskolin, isoproterenol, phosphodiesterase IV inhibitors (rolipram and Ro 20-1724), but not phosphodiesterase III inhibitors (milrinone and bemoradan). Endogenous adenosine has previously been shown to mediate FMLP-induced increases in cAMP enhanced in the presence of Ro 20-1724. In this study, adenosine deaminase prevented the inhibitory effects observed with rolipram and Ro 20-1724, implicating endogenous adenosine as a co-modulator of inhibition. FMLP stimulated neutrophil shape change and the surface expression of the beta 2 integrins CD11b/CD18 and CD11a/CD18. Both these responses were inhibited by rolipram but not bemoradan. With the use of 4,4'-diisothiocyanostilbene-2,2'disulfonic acid, we showed that mobilization of the intracellular pool of CD11b/CD18 paralleled adhesion. We conclude that neutrophil-endothelial cell adhesion is attenuated by elevating neutrophil intracellular cAMP and that inhibition of neutrophil CD11b/CD18 surface expression by cAMP accounts for this observed inhibition of adhesion.
Monoclonal IgM rheumatoid factor secreted by CD5-negative B cells during mixed cryoglobulinemia. Evidence for somatic mutations and intraclonal diversity of the expressed VH region gene.
Authors: Crouzier R , Martin T , Pasquali J L 
Published: December 2022

Abstract
Mixed cryoglobulinemia is usually considered to be a nonmalignant human B cell proliferation that produces a monoclonal IgM rheumatoid factor (RF). Important immunologic similarities and differences were described between the monoclonal B cells during mixed cryoglobulinemia and during malignant chronic lymphocytic leukemia (CLL):high frequency of the same VH and V kappa gene usage by both types of monoclonal B cells producing IgM with RF activity, apparent intraclonal homogeneity, but different expression of the pan T cell CD5 Ag. The description of an unusual CD5-negative B cell CLL case secreting a mutated IgM RF led the authors to suggest that the usage of non-mutated germline Ig genes is a property of cells derived from the CD5 lineage or stage of differentiation, rather than an intrinsic property of CLL or of IgM RF-producing cells in general. Because mixed cryoglobulinemia cells are usually CD5-negative, it was of interest to test for the existence of mutations in the VH and V kappa regions, as well as for the intraclonal homogeneity of the expressed Ig genes. In this study, we used the PCR technique to analyze the monoclonal rheumatoid factor (mRF) V genes from a patient with mixed cryoglobulinemia. We show that the CD5-negative monoclonal B cells express a slightly mutated V kappa 3 gene, but a more mutated VH1 gene whose genomic counterpart was shown to be the 51p1 germline gene. The sequence analysis of several independent clones shows some degree of intraclonal diversity, suggesting the existence of a clonal filiation. These results are discussed in terms of the origin of the monoclonal B cell during mixed cryoglobulinemia and CLL.
Co-infusion of normal bone marrow partially corrects the gld T-cell defect. Evidence for an intrinsic and extrinsic role for Fas ligand.
Authors: Sobel E S , Kakkanaiah V N , Kakkanaiah M , Cohen P L , Eisenberg R A 
Published: December 2022

Abstract
Ipr and gld mice develop systemic autoimmune diseases with nearly indistinguishable manifestations, including the accumulation of massive numbers of CD4-CD8- T lymphocytes. In vivo chimera experiments have shown that the Ipr mutation is functionally expressed in both T and B cells. When lethally irradiated Ipr mice were given a combination of normal and Ipr bone marrow, only Ipr-derived B cells produced autoantibodies and only Ipr-derived T cells hyperproliferated. In contrast, analogous experiments with gld mice showed that the co-infusion of normal bone marrow greatly reduced autoantibody production. These results indicated that the gld B cell defect was extrinsic to those cells producing autoantibodies, in agreement with the recent molecular data showing that the normal gene products of the Ipr and gld loci form an interacting receptor-ligand pair. In the present study, we have extended our functional studies with gld mice using T cell-marked congenic donors. Lymphadenopathy was reduced three- to fourfold in gld mice given a combination of congenic normal and gld bone marrow compared with mice given gld bone marrow alone, and the absolute number of CD4-CD8- T cells was reduced by a factor of 7. Surprisingly, the residual CD4-CD8- T cells present in the mixed chimeras were derived entirely from the gld donor marrow. This suggests that the gld mutation results in both an extrinsic and intrinsic defect in T cells.
The growth response to IL-7 during normal human B cell ontogeny is restricted to B-lineage cells expressing CD34.
Authors: Dittel B N , LeBien T W 
Published: December 2022

Abstract
The growth of human B cell precursors can be supported by bone marrow (BM) stromal cells and IL-7, but the identity of the responding population is unknown. In the current study, we examined the growth characteristics of FACS-purified CD10+/CD34+/cytoplasmic mu- pro-B cells and CD10+/CD34-/cytoplasmic mu+ pre-B cells in an IL-7/BM stromal cell-dependent culture. Our results show that pro-B cells proliferate, whereas pre-B cells do not. Pro-B cell growth was dependent upon direct contact with BM stromal cells, because no growth occurred when pro-B cells were suspended in transwells above a BM stromal cell monolayer in the presence of IL-7. IL-7-stimulated pro-B cells partially differentiated into a pre-B cell population, on the basis of the loss of CD34 and terminal deoxynucleotidyl (TdT) expression, and the acquisition of cytoplasmic mu heavy chains. Examination of platelet endothelial cell adhesion molecule-1/CD31 expression on B cell precursors revealed a bimodal distribution: CD34+ pro-B cells exhibited a high density pattern and CD34- pre-B cells exhibited a low density pattern. The IL-7-induced differentiation of pro-B cells into pre-B cells included a shift from high CD31 to low CD31 expression. Interestingly, pro-B and pre-B cells expressed comparable levels of IL-7R, as determined by flow cytometry, even though pre-B cells were nonresponsive to IL-7 stimulation. Our collective results show that human pro-B cells require both IL-7 and direct contact with BM stromal cells to undergo proliferation and partial differentiation into the pre-B cell stage, whereas pre-B cells are nonresponsive to IL-7 and require other signals for their survival and growth.
CD8+ T cells specific to the exogenous antigen. Mode of antigen recognition and possible implication in immunosuppression.
Authors: Hisatsune T , Nishijima K , Kohyama M , Kato H , Kaminogawa S 
Published: December 2022

Abstract
This study demonstrates and characterizes CD8+ T cells specific to the exogenous Ag, bovine alpha s1-casein. Purified CD8+ T cells from alpha s1-casein-primed lymph node cells proliferated well in response to an alpha s1-casein derivative, trypsin-digested alpha s1-casein. CD8+ T cell repertoire for the exogenous Ag was directly demonstrated in the primary culture condition. The intact alpha s1-casein primed the responding CD8+ T cells in vivo more efficiently than the tryptic alpha s1-casein; however, the in vitro proliferative response by the intact alpha s1-casein was weaker than that of the tryptic alpha s1-casein. CD8+ T cells recognized the exogenous Ag in association with MHC class I molecules as revealed by an Ab-blocking study. The major immunodominant region for the CD8+ T cells was mapped to region 136-151 of alpha s1-casein, and peptide 136-151 primed the responding CD8+ T cells but not any CD4+ T cells. Peptide 136-151 is the CD8+ T cell-specific determinant. Upon antigenic stimulation, the exogenous Ag-specific CD8+ T cells produced a significant level of IFN-gamma, which has immune suppressive activity for IgE synthesis. Our study strongly implies that CD8+ T cells that proliferate and produce IFN-gamma in response to the exogenous Ag would play a vital role in Ag-specific immunosuppression.
CD80 (B7) and CD86 (B70) provide similar costimulatory signals for T cell proliferation, cytokine production, and generation of CTL.
Authors: Lanier L L , O'Fallon S , Somoza C , Phillips J H , Linsley P S , Okumura K , Ito D , Azuma M 
Published: December 2022

Abstract
Signals initiated through both the TCR complex and CD28 are required for optimal activation of T lymphocytes. Recently, it has been demonstrated that CD28 interacts with two different ligands, designated CD80 (B7/B7-1) and CD86 (B70/B7-2). We have produced stable transfectants that express CD80, CD86, or both ligands and have examined their ability to costimulate T cell proliferation, cytokine production, and the generation of CTL. When we used small, resting human peripheral blood T cells as responders, both CD80 and CD86 transfectants efficiently costimulated anti-CD3 mAb-induced proliferation and the secretion of IL-2 and IFN-gamma. Additionally, both CD80 and CD86 transfectants were able to generate functional CTL. The magnitude and kinetics of these responses were similar, which indicates that both ligands provide efficient costimulatory signals. Because many APCs coexpress both CD80 and CD86, we compared the ability of anti-CD80 and anti-CD86 mAbs to inhibit allogeneic MLR stimulated with B lymphoblastoid cell lines and showed that it is necessary to inhibit interactions with both ligands to optimally block CD28-dependent proliferation. Given the limited homology of CD80 and CD86, it was surprising that the binding of CD28-Ig fusion protein to CD80 and that to CD86 transfectants were essentially indistinguishable. Binding of CTLA-4-Ig fusion protein to both transfectants also was quite similar, but was of higher affinity than CD28-Ig binding. Results from these studies indicate that both CD80 and CD86 are potent and similar costimulators of T lymphocytes. Therefore, the role of CD80 and CD86 in an immune response may be determined primarily by their differential expression on APC.
Costimulation with B7-1, IL-6, and IL-12 is sufficient for primary generation of murine antitumor cytolytic T lymphocytes in vitro.
Authors: Gajewski T F , Renauld J C , Van Pel A , Boon T 
Published: December 2022

Abstract
The requirements for generating CD8+ CTLs against the mastocytoma P815 were first defined by using an allogeneic mixed lymphocyte tumor culture (MLTC). Both the expansion of effector lymphocytes and the acquisition of lytic activity were dependent on the presence of accessory cells, but not CD4+ lymphocytes. Several factors were examined for their ability to replace accessory cell function. Expression of B7-1 by P815 was sufficient to induce IL-2 production by CD8+ cells, but substantial proliferation was achieved only if IL-6 was provided as well. Although IL-12 had little effect on the net proliferation of developing effector cells, it increased specific lytic activity 10-fold, acted synergistically with B7-1 in induction of IFN-gamma production during primary stimulation, and resulted in a shift toward a Th1 cytokine profile following secondary stimulation. These costimulatory factors were then studied in a primary syngeneic MLTC by using splenocytes from nonimmunized DBA/2 mice, an approach that had never before succeeded in generating specific CTLs. The combination of B7-1, IL-6, and IL-12 was sufficient to induce P815-specific CTL activity after a 5-day MLTC, which was expanded optimally following secondary stimulation in the presence of B7-1, IL-2, and IL-7. The irrelevant syngeneic tumor L1210, constructed to express B7-1 and the P815-derived tumor Ag gene P1A, also generated CTLs that lysed the parental P815. The combination of B7-1, IL-6, and IL-12 should be useful in the derivation of other tumor-specific CTLs in vitro, and may constitute the optimal stimuli for rapid proliferation and differentiation of helper-independent, tumor-specific CTLs in vivo.
T helper 2 cells are subject to high dose oral tolerance and are not essential for its induction.
Authors: Garside P , Steel M , Worthey E A , Satoskar A , Alexander J , Bluethmann H , Liew F Y , Mowat A M 
Published: December 2022

Abstract
Oral administration of aqueous protein Ag results in profound immunologic tolerance, and it has been suggested previously that this reflects selective activation of Th subsets. Here we show that the induction of oral tolerance by feeding a single high dose of OVA to mice significantly reduces the production of both Th1- and Th2-dependent cytokines and is accompanied by a marked reduction of specific Abs of both the IgG2a and IgG1 isotypes in vivo. Oral tolerance was also induced normally in IL-4-deficient mice. These results indicate that both subsets of the Th cell are equally susceptible to the induction of tolerance with a single high dose of Ag delivered via the oral route and that this phenomenon does not require Th2 cells.
Overexpression of activation transcriptional factor 1 in lymphomas and in activated lymphocytes.
Authors: Hsueh Y P , Lai M Z 
Published: December 2022

Abstract
cAMP-regulated gene expression always involves a conserved cAMP-responsive element (CRE) present in the promoter of cAMP-inducible genes. Two of the highly related proteins, cyclic AMP-responsive element binding protein (CREB) and activation transcriptional factor 1 (ATF-1), have been shown to activate transcription in response to cAMP by interacting with CRE. However, ATF-1 is a much weaker mediator of cAMP response, and its functional role in vivo remains unclear. Here we report a significant enhancement of ATF-1 expression in most transformed lymphocytes. Little variation in CREB level was observed, however. The activation of normal T lymphocytes induced a transient increase of ATF-1 expression to a level comparable to that of T lymphomas. Activation had no effect on the ATF-1 level of transformed T lymphocytes. The induction of ATF-1 required the costimulation of normal T lymphocytes with TPA and A23187. TPA, Ca2+ ionophore, or cAMP alone did not stimulate ATF-1 expression in normal lymphocytes. Nuclear run-on assay indicates that the increased ATF-1 expression in T cell lymphomas and in activated splenic T lymphocytes was not due to an enhanced transcription. Instead, an increase in ATF-1 mRNA stability was found in these lymphocytes. The regulation of ATF-1 expression through RNA stability in cells of different states suggests that ATF-1 may play an active role in cell growth and differentiation.
Regulation of germinal center B cell differentiation. Role of the human APO-1/Fas (CD95) molecule.
Authors: Lagresle C , Bella C , Daniel P T , Krammer P H , Defrance T 
Published: December 2022

Abstract
We previously described the existence of a tonsillar IgD- B cell subset with memory B cell features. To test the possibility that these cells could derive from germinal center (GC) B cell precursors, we examined the proliferation, differentiation, and phenotype of GC B cells after culturing with either anti-CD40 Abs or activated T cells, presumably mimicking the signals received by centrocytes in the light zone of GC. We show in this work that GC B cells proliferate and secrete Igs in both activation systems, thus indicating that CD40 ligation is also required for differentiation of GC B cells along the plasmacytoid pathway. T cell-dependent activation of GC B cells induced down-regulation of most GC-related markers (CD10, CD38, and CD77) and up-regulation of CD44 and CD62-L which are both expressed on the putative memory B cells subset. Moreover, T cell-mediated stimulation of GC B cells resulted in the strong induction of CD5 and up-regulation of APO-1/Fas (CD95). In contrast, stimulation performed with immobilized anti-CD40 Abs did not affect expression of CD10 and CD38 and failed to induce CD62-L and CD5, suggesting that the CD40 signaling pathway is necessary but not sufficient for the development of memory B cells. CD95 ligation on GC B cells was found to antagonize the stimulatory effect of immobilized anti-CD40 Abs on their proliferation, survival, and Bcl-2 expression. The possible role of CD95 in the expansion and selection of the Ag-activated B cell clones in GC is discussed.
Identification of the TS2/18-recognized epitope on the CD2 molecule as a target for suppression of T cell cytokine synthesis.
Authors: Schwarz M , Bohuslav J , Majdic O , Stockinger H , Knapp W , Holter W 
Published: December 2022

Abstract
CD2 mAb can inhibit T cell activation, but the mechanisms involved are still unclear. In this study, we identify the mAb TS2/18, previously reported to bind to an epitope on the distal domain of the CD2 molecule at amino acids 87-99 (1), as a particularly potent inhibitor of T cell cytokine synthesis. Although TS2/18 is comitogenic with the CD2R mAb VIT13, this mAb combination does not induce the secretion of substantial amounts of cytokines. When added to T cells stimulated with the CD2 mAb pair OKT11-VIT13, TS2/18 efficiently blocks the induction of cytokine synthesis induced by that CD2 mAb pair, although it does not interfere with the binding of OKT11. In addition, TS2/18 inhibits the increase in protein tyrosine phosphorylation and the accumulation of phosphatidic acid induced by either OKT11-VIT13 or a cross-linked CD3 mAb. Finally, TS2/18 disrupts CD2 clusters induced by the CD2 mAb pair OKT11-VIT13. We conclude that TS2/18 blocks T cell cytokine synthesis by interfering with early signal transduction, possibly by impairing the formation of signal-transducing molecule complexes on the T cell surface. Together, these data identify the CD2 epitope recognized by the mAb TS2/18 as a candidate epitope for T cell-specific immunosuppressive ligands.
Commitment and maintenance of the alpha beta and gamma delta T cell lineages.
Authors: Sim G K , Olsson C , Augustin A 
Published: December 2022

Abstract
We have generated transgenic mice using a rearranged, functional TCR-gamma gene that lacks the C gamma 1 3' silencer element, together with a TCR-delta cDNA construct designed for expression in lymphoid cells. All transgenic mice that descended from nine founders expressed alpha beta T cells and elevated levels of gamma delta T cells at various ratios. This observation does not support the proposal that alpha beta T cells are generated from T precursors in which C gamma 1 genes have been repressed via the cis-acting 3' silencer element, but it supports the idea that lineage commitment occurs independently of TCR gene expression. In seven transgenic lines, despite the absence of the 3' C gamma 1 silencer on the gamma transgene, the transgenic TCR is expressed only in gamma delta and not in alpha beta T cells. In the other two lines, in addition to T cells that express either the alpha beta or gamma delta TCR, a substantial fraction of T cells expresses both alpha beta and gamma delta TCR. These two lines also carry the highest number of copies of TCR-gamma transgene. However, in general, there is no correlation between the copy number of the gamma transgene and the fraction of T cells expressing the gamma delta TCR. The implications of these data are discussed.
Structural and phylogenetic analysis of the MHC class I-like Fc receptor gene.
Authors: Kandil E , Noguchi M , Ishibashi T , Kasahara M 
Published: December 2022

Abstract
The intestinal epithelium of neonatal mice and rats expresses an Fc receptor that mediates selective uptake of IgG in mothers' milk. This receptor (FcRn), which helps newborn animals to acquire passive immunity, is an MHC class I-like heterodimer made up of a heavy chain and beta 2-microglobulin. In the present study, we determined the genomic structure of a mouse gene (Fcrn) encoding the heavy chain of FcRn. The overall exon-intron organization of the Fcrn gene was similar to that of the MHC class I gene, thus providing structural evidence that Fcrn is a bona fide class I gene. The 5'-flanking region of the Fcrn gene contained the binding motifs for two cytokine-inducible transcription factors, NF-IL6 and NF1. However, regulatory elements found in MHC class I genes (enhancer A, enhancer B, and the IFN response element) were absent. Phylogenetic tree analysis suggested that, like the MICA, AZGP1, and CD1 genes, the Fcrn gene diverged from MHC class I genes after the emergence of amphibians but before the split of placental and marsupial mammals. Consistent with this result, Southern blot analysis with a mouse Fcrn cDNA probe detected cross-hybridizing bands in various mammalian species and chickens. Sequence analysis of the Fcrn gene isolated from eight mouse strains showed that the membrane-distal domain of FcRn has at least three amino acid variants. The fact that Fcrn is a single copy gene indicates that it is expressed in both the neonatal intestine and the fetal yolk sac.