bluuebunny/crossref_metadata_2025_split huggingface dataset:
T helper 1 response against Leishmania major in pregnant C57BL/6 mice increases implantation failure and fetal resorptions. Correlation with increased IFN-gamma and TNF and reduced IL-10 production by placental cells.
Authors: Krishnan L , Guilbert L J , Wegmann T G , Belosevic M , Mosmann T R 
Published: January 2023

Abstract
Maternal immune responses can influence fetal survival and several cytokines have harmful or protective effects on pregnancy. The Th1 cytokines IFN-gamma and IL-2 can cause fetal loss, whereas the Th2 cytokine IL-10 is protective. However, infections such as leishmaniasis show the opposite pattern: resistance is associated with the preferential mounting of a Th1 response, whereas a Th2 response exacerbates the disease. We therefore asked whether the curative Th1 response against Leishmania major in genetically resistant C57BL/6 mice, would compromise concurrent pregnancy. The number of resorptions as assessed by uterine scars was significantly increased in infected C57BL/6 mice and this was associated with a decreased production by placental cells of the Th2 cytokines IL-4 and IL-10 and increased production of IFN-gamma and TNF. Interestingly, the frequency of pregnancy failure before implantation in C57BL/6 mice was also substantially increased. In contrast to C57BL/6 mice, early infection did not reduce implantations in BALB/c mice that mount a Th2 anti-L. major response and succumb to infection. For both resorptions and implantations, there appeared to be a short period early in infection that was detrimental to pregnancy, followed by a period with lesser effects, and a later period that again induced higher resorptions or pre-implantation losses. These results suggest that a beneficial anti-parasite Th1 response can adversely affect pregnancy outcome. Furthermore, Th1 cytokines may be deleterious for not only placental maintenance but also preimplantation events.
Listeria monocytogenes induces apoptosis of infected hepatocytes.
Authors: Rogers H W , Callery M P , Deck B , Unanue E R 
Published: January 2023

Abstract
Infection with blood-borne Listeria monocytogenes results in their early uptake by the liver. Foci of hepatocytes become heavily infected and develop into microabscesses. Infection results in apoptosis of the hepatocytes. This is particularly evident in the edge of the microabscess, where hepatocytes are not yet destroyed by the neutrophil. It is also apparent when neutrophils are depleted from the circulation. Infection of hepatocytes in culture induces their death by apoptosis with the release of neutrophil chemoattractants. Cytokines do not reduce the multiplication of Listeria in cultured hepatocytes. This study calls attention to an early program of inflammation induced in infected cells that are unresponsive to cytokines.
Beta-chemokine TCA3 binds to mesangial cells and induces adhesion, chemotaxis, and proliferation.
Authors: Luo Y , Dorf M E 
Published: January 2023

Abstract
Specific receptors for the beta-chemokine TCA3 have been identified on mouse monocyte/macrophage cell lines and on mouse mesangial cells. Using Scatchard plot analysis with 125I-labeled TCA3, a single high-affinity receptor (3-4 nM) was identified. Cells of the monocyte lineage express 1,400 to 8,600 TCA3 binding sites, while mesangial cells display 40,000 to 49,000 sites/cell. Competitive inhibition studies indicated that the TCA3 receptor is unique, although MCP-1, IL-8, and RANTES were weak competitors of TCA3 binding. We also established the functional activity of TCA3 and other chemokines on primary cultures of mouse mesangial cells. TCA3 treatment induces increased mesangial cell adhesiveness to fibronectin. TCA3 is also a chemoattractant for mesangial cells. In addition, TCA3 treatment stimulates [3H]thymidine uptake by mesangial cells. The combined results indicate that TCA3 and other chemokines interact with a broader range of target cells than previously considered.
Signaling by hemolytically inactive C5b67, an agonist of polymorphonuclear leukocytes.
Authors: Wang C , Gerard N P , Nicholson-Weller A 
Published: January 2023

Abstract
The hemolytically inactive complement component complex C5b67, designated iC5b67, can signal human polymorphonuclear leukocytes (PMN) both as a pertussis toxin-inhibitable agonist for chemotaxis and as an antagonist for C5a- and FMLP-stimulated chemotaxis and superoxide production. The signaling pathways utilized by iC5b67 have been further investigated. In contrast to mastoparan, iC5b67 failed to directly activate G proteins to stimulate inositol phosphate formation in COS cells that had been transfected with G alpha 16. In COS cells co-transfected with both G alpha 16 and the C5a receptor, iC5b67 could neither activate phospholipase C nor inhibit C5a receptor-mediated activation of phospholipase C. iC5b67 stimulated GTPase activity in a membrane-enriched fraction from PMN. These data support the hypothesis that iC5b67 signals through a unique receptor, likely G protein linked, but distinct from the C5a receptor. iC5b67 was able to mobilize intracellular stores to elicit increases in intracellular Ca2+. Based on the effects of herbimycin A, wortmannin, and chelerythrine on iC5b67-induced PMN chemotaxis, iC5b67 signaling involved activation of tyrosine and phosphatidylinositol 3-kinases, but not protein kinase C. Relevant to the capacity of iC5b67 to antagonize PMN superoxide production, iC5b67 induced rapid and sustained increases in intracellular cAMP, which others have shown can inhibit superoxide formation. Although iC5b67 antagonizes C5a and FMLP receptor-mediated superoxide generation, iC5b67 had no effect on PMA-induced superoxide formation. The distinct agonist and antagonist signaling pathways activated by iC5b67 in the PMN diverge soon after initial iC5b67 receptor-mediated transduction steps.
An antibody that binds domain 1 of CD4 inhibits replication of HIV-1, but not HTLV-I, in a CD4-positive/p56lck-negative HTLV-I-transformed cell line.
Authors: Lemasson I , Briant L , Hague B , Coudronnière N , Heron L , David C , Rebouissou C , Kindt T , Devaux C 
Published: January 2023

Abstract
mAbs that bind to the Ig CDR3-like region in D1 domain of the CD4 molecule can inhibit the HIV-1 life cycle in CD4-positive T cells and lymphoblastoid cell lines at the stage of transcription. This antiviral effect requires the integrity of the cytoplasmic tail of CD4, which acts as a signal transduction region through its association with protein tyrosine kinases such as p56Ick. Here we investigated the role of p56Ick in the cascade of molecular events that control HIV-1 transcription in cells treated with anti-CD4 mAb directed against the Ig CDR3-like region. The Ig CDR3-like region-specific mAb, 13B8-2, blocked HIV-1 production in CD4-positive/p56Ick-negative HTLV-I-producing MT2 cells superinfected by HIV-1Lai, but had no effect on HTLV-I production, although it did inhibit Tax-induced NF-kappa B translocation. These results raise the possibility that an as yet unidentified tyrosine kinase may be capable of associating with CD4 and mediating intracellular signaling.
B cells are generated throughout life in humans.
Authors: Nuñez C , Nishimoto N , Gartland G L , Billips L G , Burrows P D , Kubagawa H , Cooper M D 
Published: January 2023

Abstract
This analysis of B cell development as a function of age reveals a relatively widespread distribution of progenitor B (pro-B), pre-B, and B cells in fetal tissues, and thus supports the idea of a multifocal origin of B lineage cells during embryonic development. From mid-gestation onward, the bone marrow is the major site of B cell generation in humans. A relatively constant ratio of bone marrow precursors to B cells of immature phenotype (CD24highCD10+CD20lowIgD-) is maintained from mid-gestation through the eighth decade of life. The persistence of recombinase gene activity in pro-B cells further attests the sustained production of B cells in bone marrow. Interestingly, a subpopulation of B cells with mature phenotype (CD24lowCD10-CD20highIgD+) accumulates in the bone marrow during childhood, and this becomes the predominant B cell subpopulation in adult bone marrow. This mature population of bone marrow B cells may represent a subpopulation of recirculating B cells that have undergone selection in the periphery.
The role of CD28 costimulation in immune-mediated responses against mouse mammary tumor viruses.
Authors: Palmer L D , Saha B , Hodes R J , Abe R 
Published: January 2023

Abstract
Infectious mouse mammary tumor viruses (MMTV) encode superantigens (SAg) which, when presented in association with permissive class II MHC molecules, are recognized by those T cells that express appropriate TCRs. Recent findings have indicated that expression of a permissive MHC class II product and of a specific TCR are also critical to susceptibility of newborn mice to infection with milk-borne MMTV, suggesting that SAg-mediated T cell activation may play a facilitating role in viral infection. Because effective Ag-specific T cell activation can require costimulatory signals in addition to TCR-mediated recognition, the role of the CD28 costimulatory receptor was analyzed in responses of neonatal and adult mice to MMTV challenge. Mice that were deficient in CD28 expression as a result of gene targeting were compared with CD28-intact littermates. In response to parenteral challenge with MMTV, CD28-deficient adult mice exhibited reduced expansion of MMTV SAg-reactive T cells in draining LNs, decreased cytokine production, and decreased B cell activation and Ig secretion. These results indicate that optimal T and B cell responses to MMTV challenge, as reflected in the parameters measured, are CD28 dependent. In contrast, CD28 absence did not impair TCR-V beta-specific clonal deletion induced by neonatal exposure to MMTV. Further, analysis of susceptibility to viral infection in neonatally exposed mice revealed that CD28 deficiency did not interfere with SAg-dependent MMTV infection. Failure to identify CD28 dependence of MMTV infection suggests either the absence of a costimulatory requirement in the events that lead to viral infection or a redundancy in costimulatory signals that support infection.
Phenotype and function of CD4+ T cells in mice lacking invariant chain.
Authors: Wong P , Rudensky A Y 
Published: January 2023

Abstract
Mice bearing a targeted disruption of the gene encoding the invariant chain (Ii) have provided a deeper understanding of the critical role that Ii plays in the assembly, transport, and peptide occupancy of MHC class II molecules. In this study, we have investigated the consequence of the altered class II expression in Ii-deficient (Ii zero) mice on the phenotype and function of their CD4+ T cells. As seen by others, these mice show a sharp reduction in the CD4+8- subset in the thymus and periphery. Furthermore, a large proportion of the peripheral CD4+, but not CD8+, T cells in Ii zero mice exhibit decreased surface TCR-alpha beta levels and express markers of T cell activation. Although the CD4+ T cells respond to mitogens, anti-CD3 mAbs, and alloantigens, they respond poorly to the bacterial superantigen staphylococcal enterotoxin B and do not respond to peptide and protein Ags. Analysis of reciprocal radiation bone marrow chimeras constructed using Ii zero and wild-type mice indicate that the lack of Ii in the thymus is responsible for the phenotype of the CD4+ T cells in mutant mice. These results suggest that the altered thymic peptide repertoire displayed by class II molecules in the absence of Ii has a dramatic impact on the selection of CD4+ T cells and their phenotype in the periphery.
The sheep Ig variable region repertoire consists of a single VH family.
Authors: Dufour V , Malinge S , Nau F 
Published: January 2023

Abstract
Nine germ-line Ig heavy chain variable (VH) segments (including three pseudogenes) were isolated from a genomic DNA library, and the other six were obtained by PCR, using 5'and 3' primers deduced from the first three. They appear to belong to a homogeneous VH gene family, with &gt;80% sequence identity. This sheep VH gene family is related to the human VH4 family and to the murine VH1 subgroup (clan II). Southern blot analysis shows a maximum of 10 positive restriction fragments; therefore, the nine VH genes isolated probably constitute the major part of the repertoire. Thirty-one expressed mu variable regions (and one gamma 1 variable region) were obtained from adult spleen by either cDNA cloning or anchored reverse transcriptase-PCR; they are &gt;80% similar to each other (in their leader to framework 3 regions) and to the germ-line sequences as well. The sheep VH repertoire thus seems to derive from a small (approximately 10 members) germ-line gene family, and its diversification must rely chiefly on junctional (D and/or N regions) diversity and somatic hypermutations.
Residues near the amino and carboxyl termini of staphylococcal enterotoxin E independently mediate TCR V beta-specific interactions.
Authors: Lamphear J G , Mollick J A , Reda K B , Rich R R 
Published: January 2023

Abstract
Previous studies identified three COOH-terminal residues in staphylococcal enterotoxin E (SEE; Asp200, Pro206, and Asp207) that in part mediate TCR V beta recognition. We have identified an additional three residues near the NH2-terminus of SEE (Arg20, Asn21, and Ser24 that are needed in conjunction with these COOH-terminal residues to fully restore native levels of V beta-specific T cell proliferation. A staphylococcal enterotoxin A SEA-SEE hybrid molecule containing the NH2-terminal V beta determinants of SEE to activate alone exhibited V beta specificities of both SEA and SEE, indicating that these residues of SEE independently contribute to V beta recognition and do not obscure the native V beta determinants of SEA. These findings suggest that the ability of SEE to activate certain V beta-specific T cell subsets may result from multiple interactions with a single TCR beta-chain or perhaps by cross-linking two TCR. High affinity binding to HLA-DR1, a property of native SEA, was not altered in the SEA-SEE hybrid enterotoxins containing amino acid substitutions in regions 20 to 24 and 200 to 207, indicating that residues comprising the V beta determinants of SEE are separate from residues that contribute to HLA-DR1 binding affinity. Computer models of the predicted structure of SEE revealed that the V beta determinants of SEE are located on two adjacent solvent-exposed loops. Thus, the residues of SEE that mediate V beta recognition may coalesce to form a TCR binding site with specificities for multiple TCR beta-chains.
Identification of a contact region for peptide on the TAP1 chain of the transporter associated with antigen processing.
Authors: Nijenhuis M , Schmitt S , Armandola E A , Obst R , Brunner J , Hämmerling G J 
Published: January 2023

Abstract
The transporter associated with Ag processing (TAP) translocates cytosolic peptides into the endoplasmic reticulum for presentation by MHC class 1 molecules. Recently, the actual peptide translocation step has been suggested to be preceded by binding of the peptide to TAP. In this study, we investigated the peptide binding site of TAP and its relevance for peptide selection by cross-linking of translocatable peptides. Our data demonstrate, first, that for a TAP heterodimer containing the rat TAPu allelic product, which selects peptides on basis of their C terminus, the translocation efficiency correlates with the peptide binding efficiency. Second, peptides having the cross-linker at different positions all label both the TAP1 and the TAP2 subunit after binding to the heterodimer, indicating that both TAP subunits contribute directly to the peptide binding site and contact most or all amino acids of a bound peptide. Third, by enzymatic digestion and the use specific antisera, we identified a domain of human TAP1 that contributes to the peptide binding site. This domain contains the two hydrophobic and thus putative transmembrane regions closest to the ATP binding sites. We conclude that the peptide binding site controls the selectivity of TAP and is composed of domains of both TAP1 and TAP2, which each contact the bound peptide over all or most of its length. Moreover, the major contact site(s) for peptide on TAP1 are located within or close to the two putative transmembrane regions adjacent to the ATP binding site.
Variation in HLA-DM expression influences conversion of MHC class II alpha beta:class II-associated invariant chain peptide complexes to mature peptide-bound class II alpha beta dimers in a normal B cell line.
Authors: Ramachandra L , Kovats S , Eastman S , Rudensky A Y 
Published: January 2023

Abstract
The maturation of invariant chain (Ii):MHC class II complexes into peptide-loaded alpha beta dimers occurs by proteolytic removal of Ii chain and binding of antigenic peptides derived from exogenous and endogenous Ags. A fragment of the Ii chain (class II-associated invariant chain peptide (CLIP) remains associated with class II alpha beta and is an intermediate in this process. Conversion of alpha beta:CLIP complexes into alpha beta:peptide complexes is facilitated by HLA-DM. Two unique mAbs, specific for I-Ab bound to human CLIP and I-Ab bound to DR alpha peptide, were used to assess the formation of these peptide:class II complexes in a human B lymphoblastoid cell line (B-LCL) (Swei) transfected with I-A(b). In multiple independent Swei:I-Ab transfectants, the amount of human CLIP (hCLIP):I-Ab expressed was inversely proportional to the amount of DR alpha 52-68:I-Ab; quantitative differences in HLA-DM expression accounted for this phenotype. In the low DM transfectant, a substantial proportion of I-Ab, but not DR molecules, was altered structurally and unable to present native protein Ags. Addition of DM transgenes to the DM-low cells resulted in an increase in DR alpha 52-68:I-Ab coupled with a decrease in hCLIP:I-Ab complexes and restoration of exogenous protein Ag presentation. The DR5 molecules in Swei cells, which have a lower affinity for hCLIP than I-Ab, were not affected by low DM expression, suggesting that the amount of DM required for conversion of CLIP:class II to peptide:class II may depend on the affinity of the class II molecules for CLIP or DM.
LPS-dependent cyclooxygenase-2 induction in human monocytes is down-regulated by IL-13, but not by IFN-gamma.
Authors: Endo T , Ogushi F , Sone S 
Published: January 2023

Abstract
We investigated the effects of Th2 cell-associated cytokines, IL-4, IL-10, and IL-13, on prostaglandin (PG) production by human peripheral blood monocytes (HPBM) in terms of four parameters: PGE2 synthesis; cyclooxygenase activity; protein; and mRNA of two cyclooxygenase isozymes (cyclooxygenase-1 and cyclooxygenase-2). LPS-stimulated PGE2 synthesis and cyclooxygenase activity were suppressed by IL-4, IL-10, or IL-13. Furthermore, the LPS-dependent increase of cyclooxygenase activity in HPBM was attributable to cyclooxygenase-2 because it was inhibited by NS-398 (a cyclooxygenase-2-specific inhibitor). Western and Northern blot analyses revealed that the LPS-induced increases in cyclooxygenase-2 protein and mRNA were attenuated by the addition of IL-4, IL-10, or IL-13. In contrast, cyclooxygenase-1 protein and mRNA were hardly detected in monocytes that were incubated with or without LPS in the presence or absence of IL-4, IL-10, and IL-13. These results suggest that the reduction of LPS-induced PGE2 synthesis and cyclooxygenase activity by IL-4, IL-10, and IL-13 in HPBM are mainly due to the down-regulation of cyclooxygenase-2 selectively induced by LPS. Conversely, IFN-gamma, a Th1 cell-associated cytokine, did not affect PGE2 production and cyclooxygenase activity. These data suggest a mechanism for modulation of inflammation by the anti-inflammatory Th2 cell-associated cytokines but not a Th1 cell-associated cytokine.
Identification and characterization of complement C3 receptors on human astrocytes.
Authors: Gasque P , Chan P , Mauger C , Schouft M T , Singhrao S , Dierich M P , Morgan B P , Fontaine M 
Published: January 2023

Abstract
Astrocytes express C components and have been implicated as a major source of intrathecal C. To ascertain the effects of C activation on these cells, we have evaluated the expression of CR1, CR2, and CR3 (CD35, CD21, and CD11b/CD18) in primary fetal astrocytes and astrocyte cell lines. None of the astrocyte cells tested expressed CR3, whereas primary astrocytes and one of four astrocyte cell lines expressed CR1 (220 kDa), as assessed at the protein and mRNA level. Primary fetal astrocytes and all four astrocyte cell lines expressed CR2 (155 kDa). Expression of CR2 by astrocytes was confirmed at mRNA level by reverse-transcriptase PCR, using different combinations of seven specific CR2 oligonucleotides, and by partial sequencing of the astrocyte CR2 cDNA. Astrocyte CR2 cDNA presented 100% homology with the lymphocyte CR2 cDNA between the position 181 bp to 600 bp and position 1017 bp to 1347 bp. An alternative splicing pattern of exon 11, reported previously in B cells, was observed in astrocyte CR2 cDNA. Astrocyte CR2 was functional, in that it specifically bound C3d and the EBV surface protein gp340, and the binding was blocked specifically with polyclonal anti-CR2. Scatchard analysis of membrane expression of CR2 on astrocytes revealed 2000 functional sites per cell with a Kd (3 x 10(-7) M) identical with that of CR2 on B cell (Raji).
A physiologic anti-inflammatory pathway based on thrombomodulin expression and generation of activated protein C by human mononuclear phagocytes.
Authors: Grey S T , Hancock W W 
Published: January 2023

Abstract
The endothelial molecule thrombomodulin (TM) regulates hemostasis by binding thrombin and promoting conversion of protein C to activated protein C (aPC). Apart from its anticoagulant actions, aPC modulates mononuclear phagocyte (M phi) activation, including TNF-alpha production, indicating interrelationships of the coagulation and immune systems. While the endothelium is considered to be the prime regulator of aPC generation, TM recently has been identified M phi and neutrophils. This study analyzes TM membrane expression by human blood monocytes, alveolar macrophages, and U937 cells cultured in the presence of various stimuli. All except U937 cell expressed high levels of surface TM. Surprisingly, stimulation with LPS or TNF-alpha further up-regulated TM expression by M phi, whereas cultured endothelial cells (EC) showed decreased TM expression. However, noninflammatory stimuli induced qualitatively similar changes in M phi and EC; all-trans retinoic acid and prostaglandin E up-regulated surface TM, and PMA decreased TM expression. Changes in M phi TM expression were accompanied by alteration in functional activity. Thus, LPS increased the TM cofactor activity of THP-1 cells by 27 +/- 6.9% (p &lt; 0.05), and PMA decreased their cofactor activity by 53.2 +/- 11.5% (p &lt; 0.05).In addition, in vivo relevance was demonstrated by the presence of TM on intragraft inflammatory M phi during cardiac rejection, whereas adjacent EC lacked TM expression. These studies demonstrate that expression of TM on human M phi is regulated differently to EC with respect to inflammatory stimuli, suggesting the potential for extravascular M phi to promote local production of aPC.