bluuebunny/crossref_metadata_2025_split huggingface dataset:
Androgens Alter the Cytokine Profile and Reduce Encephalitogenicity of Myelin-Reactive T Cells
Authors: Bebo Bruce F. , Schuster Jeanette C. , Vandenbark Arthur A. , Offner Halina 
Published: December 2022

AbstractAdoptive transfer of proteolipid protein 139–151-specific T cell lines was used to examine the role of androgens in regulating T cell cytokine secretion and the severity of experimental autoimmune encephalomyelitis (EAE) in the SJL mouse. In this study, we found that T cells from female mice transferred more severe EAE than T cells from male mice and that gender differences in clinical disease were due, at least in part, to differences in donor T cell cytokine secretion. T cell lines were selected from proteolipid protein 139–151-immunized female SJL mice in the presence or absence of exogenous androgens. Androgen-selected T cell lines secreted less IFN-γ and more IL-10 than untreated cell lines. Clinical disease induced by the adoptive transfer of androgen-selected T cell lines was less severe than disease induced with untreated T cell lines. Furthermore, androgen treatment of naive TCR transgenic T cells, during their first encounter with Ag, resulted in a shift in the balance of Th1/Th2 cytokines. This phenotype was maintained during subsequent stimulations in the absence of androgen. These results suggest that androgen present in the lymphoid microenvironment during the induction of an immune response can alter the development of effector T cells and may play an important role in governing gender differences in the immune response and susceptibility to autoimmune disorders.
μ-Surrogate Light Chain Physicochemical Interactions of the Human PreB Cell Receptor: Implications for VH Repertoire Selection and Cell Signaling at the PreB Cell Stage
Authors: Gauthier Laurent , Lemmers Bénédicte , Guelpa-Fonlupt Valérie , Fougereau Michel , Schiff Claudine 
Published: December 2022

AbstractThe surrogate light chain (SL) composed of the λ-like and VpreB polypeptides is organized as two Ig domains and an extra-loop structure. It associates to the μ-chain in preB cells. We have produced human VpreB, SL, two Fdμ (VH-CH1), and the two corresponding Fab-like (Fdμ-SL) recombinant proteins in baculovirus. The correctness of the general conformation of the proteins was assessed by epitope mapping and affinity measurements using a new batch of anti-VpreB mAbs. Plasmon resonance analysis showed that both VpreB and the entire SL associated with the Fdμ fragments, with Kd values of 3 × 10−8 M for VpreB-Fdμ and of 10−9 to 10−10 M, depending upon the VH, for SL-Fdμ. These results indicate that the λ-like chain, in addition to be covalently bound to the Cμ1 domain, also interacts with the VH domain. Therefore, a dual role of the SL emerges: 1) interaction of the C-domain of λ-like would release the μ-chain from its interaction with binding protein in the endoplasmic reticulum, and 2) interaction of a part of λ-like and most of VpreB would bind to VH, ensuring a “quality control” of the native heavy chain that represents the first step of selection of the B cell repertoire. We also demonstrated that two Fab-like fragments did not interact with each other, suggesting that activation of the cell surface preB receptor does not involve aggregation neither in cis nor in trans of the Fab-like structures.
Triggering of Chloride Ion Efflux from Human Neutrophils as a Novel Function of Leukocyte β2 Integrins: Relationship with Spreading and Activation of the Respiratory Burst
Authors: Menegazzi Renzo , Busetto Sara , Decleva Eva , Cramer Rita , Dri Pietro , Patriarca Pierluigi 
Published: December 2022

AbstractPMN residing on immobilized fibronectin have been shown to respond to TNF with an intense and long lasting Cl− efflux that leads to a marked decrease of the unusually high basal Cl− content of these phagocytes. The finding that this Cl− efflux depends, at least in part, on β2 integrin engagement stimulated the present investigation, which addresses the question as to whether β2 integrins per se, in the absence of PMN agonists, are able to generate signals triggering Cl− efflux. We induced β2 integrin cross-linking by plating PMN onto surface-bound mAbs directed against either the common β-chain (CD18) or the individual α-chains (CD11a, CD11b, CD11c) of LFA-1, CR3, and gp150/95. Anti-CD18 mAbs triggered a marked release of Cl− ions, which was accompanied by spreading and activation of the respiratory burst. Cross-linking of gp150/95 and LFA-1 generated the most powerful signals for the activation of Cl− efflux. The results of three independent experimental approaches, i.e., kinetic studies, use of Cl− transport inhibitors, and modulation of Cl− efflux with different amounts of anti-β2 integrin mAbs, indicated that Cl− efflux regulates both spreading and respiratory burst triggered by β2 integrin cross-linking. Cl− efflux appears to be independent on either alterations of [Ca2+]i or changes in the plasma membrane potential and shows sensitivity to a raise in pHi. This study uncovers a new signaling ability of β2 integrins and contributes to highlight the role of Cl− efflux in the outside-in signal transduction pathway regulating adherence-dependent PMN responses.
Complement-Mediated Anti-HIV-1 Effect Induced by Human IgM Monoclonal Antibody Against Ganglioside GM2
Authors: Wu Xiaoshan , Okada Noriko , Momota Hiroshi , Irie Reiko F. , Okada Hidechika 
Published: December 2022

Abstract
HIV-infected cells aberrantly express a high level of antigenic glycosidic structures such as GM2 and Gg4. Some normal sera containing natural IgM Abs to GM2 and/or Gg4 cause C-mediated cytolysis of HIV-infected cells. In the present study we demonstrated that a human IgM anti-GM2 mAb (L55 Ab) can induce cytolysis of HIV-infected cells. Increased GM2 expression by HIV-1 infection of a human T cell line (MOLT4), a human monocyte cell line (U937), and human lymphoblastoid cells was confirmed by immunofluorescence staining with L55 Ab. These infected cells were readily lysed by L55 Ab in the presence of fresh human serum as a C source that alone did not cause cytolysis. L55 Ab also had the ability to destroy HIV-1 particles via C-mediated lysis. By adding L55 Ab together with human C to mixed culture of HIV-infected cells and naive cells, HIV-1 replication was significantly suppressed, and this effect was synergistic when L55 Ab was combined with a reverse transcriptase inhibitor and a proteinase inhibitor. Therefore, a human IgM anti-GM2 mAb may be effective in treating HIV-infected patients, especially when used together with chemotherapeutic agents.
Selective Induction of Protective MHC Class I-Restricted CTL in the Intestinal Lamina Propria of Rhesus Monkeys by Transient SIV Infection of the Colonic Mucosa
Authors: Murphey-Corb Michael , Wilson Lawrence A. , Trichel Anita M. , Roberts Donald E. , Xu Keyu , Ohkawa Susumu , Woodson Bruce , Bohm Rudolf , Blanchard James 
Published: December 2022

Abstract
The identification of mucosal immune responses required for protection against sexual transmission of HIV is essential for the development of an efficacious vaccine. To gain a better understanding of these responses, we have characterized the immune responses in the lamina propria (LP) and epithelium of the jejunum, the mesenteric lymph nodes, and peripheral blood (PBMC) of 11 rhesus monkeys following colonic exposure to two molecular clones of SIV. Two monkeys had no signs of infection. Three monkeys became persistently infected. Transient infections, characterized by the sporadic detection of virus in the periphery and/or detection of SIV-specific immune responses in either the gut-associated tissues or PBMC, were induced in six of the monkeys. One persistently infected and three transiently infected monkeys had high levels of SIV env-specific MHC class I restricted CTL in the jejunal LP. Another transiently infected monkey had SIV-specific IgA secreting B cells in the LP. Three or six months postexposure, these animals and four naive controls were challenged intracolonically with the heterologous primary isolate, SIV/DeltaB670. All four monkeys with strong SIV env-specific MHC-restricted CTL in the LP were protected, whereas none of the naive controls or the remaining seven monkeys with little or no CTL in the LP were protected. These experiments provide the first direct evidence that transient mucosal infection can induce SIV-specific immunity that remains localized to the gut-associated tissues. Furthermore, a strong correlation between SIV env-specific MHC-restricted CTL in the LP and protection against colonic mucosal challenge was observed.
The Epitopes Targeted by the Rheumatoid Arthritis-Associated Antifilaggrin Autoantibodies are Posttranslationally Generated on Various Sites of (Pro)Filaggrin by Deimination of Arginine Residues
Authors: Girbal-Neuhauser Elisabeth , Durieux Jean-Jacques , Arnaud Michel , Dalbon Pascal , Sebbag Mireille , Vincent Christian , Simon Michel , Senshu Tatsuo , Masson-Bessière Christine , Jolivet-Reynaud Colette , Jolivet Michel , Serre Guy 
Published: December 2022

Abstract
Antifilaggrin autoantibodies (AFA) are a population of IgG autoantibodies associated to rheumatoid arthritis (RA), which includes the so-called “antikeratin” Abs and antiperinuclear factor. AFA are the most specific serological markers of RA. We previously showed that they recognize human epidermal filaggrin and other profilaggrin-related proteins of various epithelial tissues. Here, we report further characterization of the protein Ags and epitopes targeted by AFA. All the Ags that exhibit numerous neutral/acidic isoelectric variants were immunochemically demonstrated to be deiminated proteins. In vitro deimination of a recombinant human filaggrin by a peptidylarginine deiminase generated AFA epitopes on the protein. Moreover, two of three filaggrin-derived synthetic peptides with a citrulline in the central position were specifically and widely recognized by AFA affinity-purified from a series of RA sera. These results indicate that citrulline residues are constitutive of the AFA epitopes, but only in the context of specific amino acid sequences of filaggrin. In competition experiments, the two peptides abolished the AFA reactivity of RA sera, showing that they present major AFA epitopes. These data should help in the identification of a putative deiminated AFA-inducing or cross-reactive articular autoantigen and provide new insights into the pathogenesis of RA. They could also open the way toward specific immunosuppressive and/or preventive therapy of RA.
In Vitro Intrathymic Differentiation Kinetics of Human Fetal Liver CD34+CD38− Progenitors Reveals a Phenotypically Defined Dendritic/T-NK Precursor Split
Authors: Plum Jean , De Smedt Magda , Verhasselt Bruno , Offner Fritz , Kerre Tessa , Vanhecke Dominique , Leclercq Georges , Vandekerckhove Bart 
Published: December 2022

AbstractHuman CD34+CD38− hematopoietic precursor cells from fetal liver are able to develop into T, NK, and dendritic cells in a hybrid human/mouse fetal thymic organ culture (FTOC). In this report, we pay particular attention to the early events in differentiation of these precursor cells. We show that the CD34+CD38− precursor cells, which are CD4−CD7−cyCD3−HLA-DR−/++ (cy, cytoplasmatic), differentiate into a CD4+ population that remained CD7−cyCD3−HLA-DR++ and a CD4− population that expressed CD7 and cyCD3. The CD4+CD7−cyCD3− cells differentiate into phenotypically and functionally mature dendritic cells, but do not differentiate into T or NK cells. The CD4−CD7+cyCD3+ population later differentiates into a CD4+CD7+cyCD3+HLA-DR− population, which has no potential to differentiate into dendritic cells but is able to differentiate into NK cells and γδ and αβ T lymphocytes. These findings support the notion that the T/NK split occurs downstream of the NK/dendritic split.
Class I MHC Molecule-Mediated Inhibition of Sindbis Virus Replication
Authors: Hahn Young S. , Guanzon Angelo , Rice Charles M. , Hahn Chang S. 
Published: December 2022

Abstract
The threshold for systemic viral infection relies on the amplification of virus at a primary infection site. We have identified that class I MHC molecules can trigger the inhibition of replication of Sindbis virus in a haplotype- and allele-specific manner. Class I MHC molecules of H-2d haplotypes exhibit a strong inhibitory effect whereas H-2k haplotypes show minimal inhibition of Sindbis viral replication. By a single gene transfection of H-2d class I MHC molecules, into cells that express class I MHC molecules of H-2k haplotype and are susceptible to viral replication, these cells became resistant to viral replication. The inhibition of viral replication by class I MHC molecules occurs neither during the stage of virus entry/endocytosis nor during virus maturation. Rather, viral-specific RNA replication, as well as viral gene expression, are inhibited in cells expressing inhibitory class I MHC molecules. This class I MHC molecule-mediated inhibition requires newly synthesized host gene products, implying the activation of an intracellular signaling mechanism that is triggered by specific class I MHC molecules.
Mouse IL-13 Enhances Antibody Production In Vivo and Acts Directly on B Cells In Vitro to Increase Survival and Hence Antibody Production
Authors: Lai Yew Hon , Mosmann Timothy R. 
Published: December 2022

AbstractIL-13, a Th2 cytokine, exhibits similar functions to IL-4 in stimulating proliferation and class switching of human B cells. Although mouse B cells were reported to be unresponsive to IL-13, we now show that IL-13 directly stimulates mouse B cells, causing extended survival and higher Ab levels. Recombinant mouse IL-13 was administered via osmotic pump during immunization of BALB/c mice with chicken RBCs. IL-13 treatment enhanced not only the plasma levels of total IgG1, IgG2a, and IgG2b but also Ag-specific Ig levels. To examine whether IL-13 acted directly on mouse B cells, B220+ B cells were cultured with fixed, anti-CD3-activated Th2 clones. Production of IgM and IgG1 was enhanced moderately by IL-13 and strongly by IL-4. Anti-CD40-stimulated sIgD+ mouse B cells also responded to IL-13 by producing increased levels of IgM, and to a lesser extent IgG1, IgG2a, IgG2b, and IgG3. No evidence was found for IL-13-induced class switching. Mouse B cells were stimulated directly rather than indirectly via contaminating cells, as IL-13 increased the numbers of both total and Ab-secreting B cells in aliquots of 100 sIgD+ B cells (&gt;99.5% pure) stimulated with anti-CD40 Ab. Stimulation of B cells by IL-13 was unaffected by the addition of anti-IL-4 to the cultures. In contrast to IL-4, IL-13 did not increase CD23 expression or B cell proliferation as measured by dilution of an intracellular fluorescence label. Collectively, these data indicate that IL-13 can enhance mouse B cell Ab production by increasing survival of the B cells.
T Lymphocyte Development in the Absence of CD3ε or CD3γδεζ
Authors: Wang Baoping , Wang Ninghai , Whitehurst Charles E. , She Jian , Chen Jianzhu , Terhorst Cox 
Published: December 2022

AbstractCD3γ, δ, ε, and ζ proteins together with the pre-TCR α-chain (pTα) and a rearranged TCR β-chain assemble to form the pre-TCR that controls the double negative (DN) to double positive (DP) stages of thymopoiesis. The CD3 proteins are expressed before pTα and TCR β-chains in prothymocytes and are expressed intracellularly in precursor NK cells, suggesting that the CD3 complex may function independent of pTα and TCRβ. In this report, both the role of CD3ε exclusively, and the role of CD3 proteins collectively, in thymocyte and NK cell development were examined. In a mouse strain termed εΔP, a neomycin cassette inserted within the CD3ε promoter abolishes CD3ε and δ expression and also abolishes CD3γ expression in all but a small minority (≤1%) of prothymocytes. These prothymocytes became deficient in CD3ε alone upon reconstitution of CD3δ expression and were severely, but not completely, arrested at the DN stage, as small numbers of double positive thymocytes were detected. In de facto CD3γδεζnull mice generated by crossing the εΔP mice with CD3ζ−/− mice, thymopoiesis were arrested at the CD44−CD25+ DN stage as observed in RAG−/− mice, DJ and VDJ recombination at the TCRβ locus was functional, and normal numbers of NK cells were detected. Together, the findings demonstrate that during thymocyte development, the CD3 complex collectively is not essential until the critical CD44−CD25+ DN stage in which pre-TCR begins to function, whereas CD3ε is critical for the assembly of pre-TCR. Moreover, CD3 proteins are dispensable for NK cell development.
Osteopontin Is Associated with T Cells in Sarcoid Granulomas and Has T Cell Adhesive and Cytokine-Like Properties In Vitro
Authors: O’Regan Anthony W. , Chupp Geoffrey L. , Lowry John A. , Goetschkes Margo , Mulligan Niall , Berman Jeffrey S. 
Published: December 2022

AbstractSarcoidosis is a systemic disease characterized by the accumulation of activated T cells and widespread granuloma formation. In addition, individual genetic predisposition appears to be important in this disease. Osteopontin, a noncollagenous matrix protein produced by macrophages and T lymphocytes, is expressed in the granulomas of tuberculosis, and is associated with genetic susceptibility to intracellular infection. The function of osteopontin in these T cell-mediated responses is unknown. We sought to elucidate the role of osteopontin in granulomatous inflammation by characterizing its expression in different stages of sarcoidosis and its effector function on T cells in vitro. Lymphocyte-associated expression of osteopontin in sarcoidosis was demonstrated by immunohistochemistry, and its expression correlated with granuloma maturity. In addition, osteopontin induced T cell chemotaxis, supported T cell adhesion (an effect enhanced by thrombin cleavage of osteopontin), and costimulated T cell proliferation. These results suggest a novel mechanism by which osteopontin and thrombin modulate T cell recruitment and activation in granulomatous inflammation.
The Mast Cell as Site of Tissue-Type Plasminogen Activator Expression and Fibrinolysis
Authors: Sillaber Christian , Baghestanian Mehrdad , Bevec Dorian , Willheim Martin , Agis Hermine , Kapiotis Stylianos , Füreder Wolfgang , Bankl Hans C. , Kiener Hans P. , Speiser Wolfgang , Binder Bernd R. , Lechner Klaus , Valent Peter 
Published: December 2022

AbstractRecent data suggest that mast cells (MC) and their products (heparin, proteases) are involved in the regulation of coagulation and fibrino(geno)lysis. The key enzyme of fibrinolysis, plasmin, derives from its inactive progenitor, plasminogen, through catalytic action of plasminogen activators (PAs). In most cell systems, however, PAs are neutralized by plasminogen activator inhibitors (PAIs). We report that human tissue MC as well as the MC line HMC-1 constitutively produce, express, and release tissue-type plasminogen activator (tPA) without producing inhibitory PAIs. As assessed by Northern blotting, highly enriched lung MC (&gt;98% pure) as well as HMC-1 expressed tPA mRNA, but did not express mRNA for PAI-1, PAI-2, or PAI-3. The tPA protein was detectable in MC-conditioned medium by Western blotting and immunoassay, and the MC agonist stem cell factor (c-Kit ligand) was found to promote the release of tPA from MC. In addition, MC-conditioned medium induced fibrin-independent plasmin generation as well as clot lysis in vitro. These observations raise the possibility that MC play an important role in endogenous fibrinolysis.
IL-12 Is a Heparin-Binding Cytokine
Authors: Hasan Maemunah , Najjam Saloua , Gordon Myrtle Y. , Gibbs Roslyn V. , Rider Christopher C. 
Published: December 2022

AbstractUsing an ELISA approach, we demonstrate that recombinant human IL-12 (rhIL-12) binds strongly to an immobilized heparin-BSA complex. This binding is completely displaceable with soluble heparin, IC50∼ 0.1 μg/ml, corresponding to ∼ 10 nM. By interpolation with our previous findings, this indicates an affinity for heparin greater than that of antithrombin III and comparable with that of FGF-2, two high-affinity heparin-binding proteins. Recombinant murine IL-12 also binds strongly to heparin. The binding of rhIL-12 to heparin shows specificity because chondroitin sulfates A and C fail to compete, whereas chondroitin B inhibits weakly. A highly sulfated heparan sulfate is a strong competitor, whereas other heparan sulfates show weak or no activity. Small heparin fragments inhibit binding, although activity decreases with size. An octasaccharide pool derived by cleavage of heparin with nitrous acid is a significantly stronger inhibitor than its heparinase I-derived counterpart, further indicating structural specificity in the interaction between rhIL-12 and heparin. The binding of recombinant p40 to heparin appears indistinguishable from that of the IL-12 heterodimer, implying that the heparin binding site is largely if not solely located in this subunit. These results show for the first time that IL-12 is a heparin-binding cytokine, a property common to the other Th1-response-inducing cytokines, IFN-γ and IL-2. Our findings strongly suggest that IL-12 will tend to be retained close to its sites of secretion in the tissues by binding to heparin-like glycosaminoglycans, thus favoring a paracrine role for IL-12.
High Affinity Very Late Antigen-4 Subsets Expressed on T Cells Are Mandatory for Spontaneous Adhesion Strengthening But Not for Rolling on VCAM-1 in Shear Flow
Authors: Chen Chun , Mobley James L. , Dwir Oren , Shimron Frida , Grabovsky Valentin , Lobb Roy R. , Shimizu Yoji , Alon Ronen 
Published: December 2022

AbstractThe very late Ag-4 (VLA-4) integrin supports both rolling and firm adhesion of leukocytes on VCAM-1 under shear flow. The molecular basis for the unique ability of a single adhesion molecule to mediate these versatile adhesive processes was investigated. VLA-4 occurs in multiple activation states, with different affinities to ligand. In this study we tested how these states regulate VLA-4 adhesiveness under shear flow in Jurkat T cells and PBL. VLA-4 on nonstimulated Jurkat cells supported rolling and spontaneous arrest on VCAM-1, whereas a Jurkat activation mutant with reduced VLA-4 affinity failed to spontaneously arrest after tethering to or during rolling on VCAM-1. The contribution of VLA-4 affinity for ligand to rolling and spontaneous arrests on immobilized VCAM-1 was dissected using soluble VLA-4 ligands, which selectively block high affinity states. VLA-4 saturation with ligand completely blocked spontaneous adhesion strengthening post-tethering to VCAM-1, but did not impair rolling on the endothelial ligand. High affinity VLA-4 was found to comprise a small subset of VLA-4 on resting Jurkat cells and PBL. This subset is essential for firm adhesion but not for tethering or rolling adhesions on VCAM-1. Interestingly, low and high affinity VLA-4 states were found to mediate similar initial tethering to ligand. High affinity VLA-4, constitutively expressed on circulating T cells, may control their early adhesion strengthening on VCAM-1-expressing endothelium before exposure to vascular chemokines and activation of additional integrins.