bluuebunny/crossref_metadata_2025_split huggingface dataset:
Porcine endothelial CD86 is a major costimulator of xenogeneic human T cells: cloning, sequencing, and functional expression in human endothelial cells.
Authors: Maher S E , Karmann K , Min W , Hughes C C , Pober J S , Bothwell A L 
Published: December 2022

Abstract
Porcine aortic endothelial cells (PAECs), unlike human endothelial cells, express a surface protein recognized by human CTLA4Ig fusion protein that costimulates human T cells through CD28. We have cloned porcine CD86 (pCD86) from an immortalized porcine endothelial cell line, PEC-A, that expresses high levels of this CTLA-4-binding protein. pCD86 mRNA is expressed in PEC-A and PAECs but not in human endothelial cells. Expression of stably transfected pCD86 in CHO cells modestly costimulates human T cell proliferation and IL-2 secretion. Expression of transiently transfected pCD86 in human umbilical vein endothelial cells strongly costimulates IL-2 production by human T cells, comparable to costimulation by PAECs. Costimulation of human T cells by pCD86 in both systems is as effective as costimulation by human CD80 or CD86, and can be blocked by human CTLA4Ig. We conclude that pCD86 contributes to the strong xenoreactivity of porcine endothelium.
Toxic shock syndrome toxin-1-induced death is prevented by CTLA4Ig.
Authors: Saha B , Jaklic B , Harlan D M , Gray G S , June C H , Abe R 
Published: December 2022

Abstract
Lethal toxic shock syndrome (TSS) results from the MHC class II presentation of bacterial superantigens, most commonly toxic shock syndrome-1 (TSST-1), to specific TCR Vbeta-bearing T cells. This superantigen-induced stimulation of whole T cell subsets leads to the exuberant cytokine production that in turn causes the shock syndrome. Since T cell activation and cytokine production are known to be dependent upon costimulatory signals, we reasoned that interfering with costimulation could effect TSS outcome. To test that hypothesis, we evaluated the effect of CTLA4Ig, a fusion protein known to block costimulatory signaling, on TSST-1-induced responses. CTLA4Ig not only blocked TSST-1-stimulated T cell proliferation by 90% in vitro, it also strikingly ameliorated TSST-1 induced TSS in vivo. While all mice co-administered TSST-1 and control Ig died, 75% of the CTLA4Ig plus TSST-1-treated mice survived. This salutary CTLA4Ig effect correlated with markedly diminished TSST-1 induced serum levels of TNF-alpha and IFN-gamma, but TSST-1-triggered IL-2 release was not affected. Surprisingly, while CTLA4Ig treatment group survivors remained sensitive to TSS induced by an unrelated superantigen (staphylococcal enterotoxin B), they were completely resistant to a second TSST-1 challenge. Furthermore, this TSST-1 resistance could be transferred to naive C57BL/6 mice using CD8+ T cells from CTLA4Ig plus TSST-1-primed mice. These data suggest several novel interpretations: 1) that the release of TNF-alpha and IL-2 have a different costimulatory signal dependence in vivo, 2) that the TSS resistance conferred by CTLA4Ig was superantigen specific, and 3) that the delayed and transferable resistance to TSST-1 was due, at least in part, to CD8+ T cells with suppressor function.
MHC genotype controls the capacity of ligand density to switch T helper (Th)-1/Th-2 priming in vivo.
Authors: Schountz T , Kasselman J P , Martinson F A , Brown L , Murray J S 
Published: December 2022

Abstract
A quantitative mechanism for the differentiation of CD4 T cells into recognized subsets of Th1 and Th2 effectors is controversial. Here, we define the Ag dose more precisely to the density of a minimal immunogenic peptide presented on the surface of a specific APC type. Th1 and Th2 responder MHC genotypes differ by as much as an order of magnitude in the density of this peptide displayed on B7-2+ B cells. We asked whether such B cells presenting a low ligand density primed Th2 effectors in an MHC genotype with predisposed high-density presentation and Th1-type immunity, and whether high ligand density B cells primed Th1 effectors in an MHC genotype that normally presents a low density and the Th2 phenotype. While low ligand density had the capacity to switch phenotype in the Th1 responder, high-density presentation did not alter genetically determined Th2 responder status.
Apoptosis of mouse naive T cells induced by recombinant soluble Fas ligand and activation-induced resistance to Fas ligand.
Authors: Suda T , Tanaka M , Miwa K , Nagata S 
Published: December 2022

Abstract
We have investigated the susceptibility of mouse T cells at various maturation and activation stages to recombinant soluble mouse Fas ligand (termed WX1). CD4+CD8+ thymocytes were preferentially killed by WX1, although CD4+CD8- and CD4-CD8+ thymocytes were also killed at higher concentrations of WX1. The majority of CD4-CD8- thymocytes were resistant to the same doses of WX1. Naive peripheral T cells were also killed by WX1 at concentrations similar to those for single-positive thymocytes. Activation-induced cell death of previously activated T cells is known to be mediated by Fas and Fas ligand. However, the activation of naive splenic T cells by mAbs against CD3/TCR complex rather induced resistance against WX1. This resistance was induced in activated T cells but not in bystander T cells. These mechanisms seem to explain why activated T cells are not immediately killed and why bystander T cells are not activated in an Ag-nonspecific manner.
Cloning of minimally divergent allelic forms of the natural killer (NK) receptor Ly-49C, differentially controlled by host genes in the MHC and NK gene complexes.
Authors: Sundbäck J , Kärre K , Sentman C L 
Published: December 2022

Abstract
We have investigated whether expression of Ly-49C, detected by the mAb SW5E6, is subject to similar regulation by host MHC as is Ly-49A. Ly-49C expression was regulated by host MHC differentially in mice of A/Sn (A) and C57BL/6 (B) origin. Analysis of AXB recombinant inbred strains suggested two loci regulating the expression, one segregating with the NK gene complex and the other with the MHC. In MHC congenic strains, the A form of Ly-49C had a low expression level and was further down-regulated in the presence of the H-2b haplotype (very low). The B form of Ly-49C had a high expression level and was down-regulated in the presence of H-2Kk (medium). To test the hypothesis that the Ly-49C receptor in A/Sn and C57BL/6 mice may be differentially regulated by MHC products because they represent allelic forms, cDNAs for Ly-49C were cloned by reverse-transcriptase PCR from A/Sn and C57BL/6 mouse strains. The Ly-49C sequences from the two strains differed by six nucleotides leading to four predicted amino acid changes. Both cDNAs could be detected by the Ly-49C-specific Ab when expressed in EL-4 cells. Thus, like Ly-49A, Ly-49C expression is regulated by MHC class I molecules. Furthermore, A/Sn and C57BL/6 mice express different forms of Ly-49C that are down-regulated by different MHC class I molecules.
Lack of requirement for SHP-1 in both Fas-mediated and perforin-mediated cell death induced by CTL.
Authors: Takayama H , Lee M H , Shirota-Someya Y 
Published: December 2022

Abstract
The Fas (CD95)-transmitted cell death signal has been reported to involve a protein tyrosine phosphatase, SHP-1. We analyzed the role of SHP-1 in the Fas-dependent as well as the perforin-dependent pathways of CTL-mediated killing using target cells prepared from SHP-1-deficient motheaten mice. Con A blast targets prepared from both a motheaten mouse and a phenotype-normal littermate were equally sensitive to the cytolysis and DNA fragmentation induced by both perforin-deficient Fas-dependent CTL and Fas ligand-deficient perforin-positive CTL. Fas-induced DNA degradation detected by the terminal deoxynucleotide transferase reaction was also observed in the killing of motheaten thymocytes by a Fas-based CTL as well as by anti-Fas mAb. These data cast doubt on the involvement of SHP-1 in Fas-induced lymphoid cell death.
Mutations in the MHC class II binding domains of staphylococcal enterotoxin A differentially affect T cell receptor Vbeta specificity.
Authors: Newton D W , Dohlsten M , Olsson C , Segrén S , Lundin K E , Lando P A , Kalland T , Kotb M 
Published: December 2022

Abstract
C-terminal residues of staphylococcal enterotoxin A (SEA), including H187, D225, and D227, are involved in moderate affinity binding to MHC class II beta-chain, whereas N-terminal residues, including F47, are involved in low affinity binding to MHC class II alpha-chain. The effect of alanine substitutions at residues D227 or F47 on induction of T cell proliferation and the expansion of specific TCR Vbeta families was determined. SEA wild type specifically activated T cells expressing Vbeta1, Vbeta5.2, Vbeta6, Vbeta7, Vbeta9, Vbeta18, and Vbeta22. Although SEA-D227A exhibited substantially reduced mitogenicity compared with SEA wild type, it expanded the same Vbeta-bearing T cells, except those expressing Vbeta1. By contrast, SEA-F47A, which was slightly less mitogenic than SEA wild type, induced expansion only of T cells expressing Vbeta6, Vbeta7, and to a lesser extent Vbeta22. Therefore, specific mutations affecting either MHC class II alpha or beta binding sites differentially affect the Vbeta specificity of this superantigen. The lack of expansion in four of seven Vbeta families by SEA-F47A suggests that the class II alpha binding site may position SEA on the MHC class II molecules in an appropriate conformation for interaction with certain Vbeta elements.
The progeny of a single virgin B cell predominates the human recall B cell response to the capsular polysaccharide of Haemophilus influenzae type b.
Authors: Barington T , Hougs L , Juul L , Madsen H O , Ryder L P , Heilmann C , Svejgaard A 
Published: December 2022

Abstract
Restricted V region diversity is a key feature of Abs to many haptens and simple polysaccharides. Two possible mechanisms exist: 1) selection of many clonally unrelated B cells using very similar or identical VDJ and VJ rearrangements; and 2) selection of a heavily expanded progeny of few virgin B cells. How many virgin B cells eventually give rise to the total Ab response to a simple Ag is a fundamental immunologic question. In this report, we address this question in human adults by analyzing the rearranged VkappaJkappa genes of B cells responding to a single dose of the capsular polysaccharide of Haemophilus influenzae type b coupled to tetanus toxoid. We combined affinity purification of circulating vaccine-induced Ab-secreting cells with PCR amplification of cDNA followed by cloning and sequencing. Forty-eight and 42 kappa VJ gene transcripts were analyzed from two adults, respectively. Both individuals used extremely restricted repertoires with &gt;90% of the cells using a single Vkappa gene rearranged to a single Jkappa gene. Despite the fact that the Ab responses engaged high numbers of Ab-secreting cells, analysis of the many shared, somatically acquired mutations showed that the majority of the cells originated from a common virgin B cell. Kinetic considerations implied that an extremely selected population of hypermutated memory B cells must have existed in these individuals before the first systemic immunization with the Ag. A possible role for the mucosal immune system in the priming and selection of these cells is proposed.
Cytokine expression by human peripheral blood dendritic cells stimulated in vitro with HIV-1 and herpes simplex virus.
Authors: Ghanekar S , Zheng L , Logar A , Navratil J , Borowski L , Gupta P , Rinaldo C 
Published: December 2022

Abstract
Dendritic cells are potent stimulators of Ag-specific T cell responses and have been implicated in the pathogenesis of HIV-1 and other viral infections. Although cytokines may be involved in both of these processes, there is little information on the expression of cytokines by human blood dendritic cells. We characterized cytokine gene and protein expression in dendritic cells that were purified from normal human PBMC by flow cytometry and stimulated in vitro for up to 24 h with HIV-1 or herpes simplex virus (HSV). The unstimulated, uncultured dendritic cells were defined by their phenotype (HLA DR+ CD3- CD19- CD16- CD56- CD14-) and distinct morphology, lack of mRNA expression for CD3, CD14 and CD19, and presence of mRNA for CD4 and CD83. The purified dendritic cells also expressed CD4 (70-90%), CD33 (36-48%), and CD11c (44-54%); lacked CD1a expression (&lt;1%); and were potent stimulators of an allogeneic MLR. The stimulated dendritic cells expressed mRNA for IFN-alpha, IL-1alpha, IL-1beta, IL-6, IL-10, IL-12, GM-CSF, and TNF-alpha within 4 to 12 h as determined by reverse transcription-PCR, with higher levels induced by HSV compared with HIV-1 strains IIIb or BaL. In contrast, the dendritic cells produced detectable protein only for IFN-alpha and IL-6 in response to HIV-1 or HSV, and IL-1beta in response to HSV within 24 h. There were no differences in expression of CD80 and CD86 surface molecules by dendritic cells that were either mock stimulated or stimulated with HIV-1 or HSV for 24 h. Production of IFN-alpha, IL-1beta, and IL-6 by dendritic cells may be important to the immunologic function of these cells and their role in the pathogenesis of HIV-1 and HSV infections.
The role of E-selectin in lymphocyte and polymorphonuclear cell recruitment into cutaneous delayed hypersensitivity reactions in sensitized pigs.
Authors: Binns R M , Whyte A , Licence S T , Harrison A A , Tsang Y T , Haskard D O , Robinson M K 
Published: December 2022

Abstract
We have studied the role of E-selectin in leukocyte accumulation into Ag-specific cutaneous delayed-type hypersensitivity reactions in pigs sensitized to the topical application of 2,4-dinitro-1-fluorobenzene or to the intradermal injection of bacillus Calmette-Guérin. The delayed-type hypersensitivity reactions were shown to be specific for the sensitizing Ag and characterized by the up-regulation of E-selectin, as demonstrated by the uptake of tracer 99mTc-labeled monoclonal anti-E-selectin mAb and entry of 51Cr-labeled PBL and (111)In-labeled polymorphonuclear cells (PMN). Intravenous injection of 5 mg/kg of a F(ab')2 preparation of a monoclonal anti-E-selectin Ab at peak times of leukocyte entry resulted in a significant inhibition of entry of both PMN and lymphocytes. The anti-E-selectin Ab inhibited PMN recruitment by 70 to 90% and lymphocyte recruitment by 50 to 60%. In comparison, an anti-CD18 treatment reduced PMN recruitment by 70 to 90% and lymphocyte recruitment by 60 to 70% in this model. These data confirm an important role for E-selectin in the recruitment of both PMN and lymphocytes to sites of immune-based dermal inflammation.
Monocytes can phagocytose Gram-negative bacteria by a CD14-dependent mechanism.
Authors: Grunwald U , Fan X , Jack R S , Workalemahu G , Kallies A , Stelter F , Schütt C 
Published: December 2022

Abstract
Phagocytosis of bacteria by monocytes and neutrophil granulocytes provides an important first line of defense against bacterial infections. Opsonization of bacteria with complement and phagocytosis by neutrophils is dependent on divalent cations and does not take place in blood that has been anticoagulated with EDTA. Monocytes, however, do carry out phagocytosis even in the presence of EDTA. We show here that this divalent cation-independent phagocytosis pathway requires the presence of the LPS receptor CD14 on the cell surface. This pathway is dependent on the availability of LPS binding protein, can be blocked by anti-CD14 Abs, by an excess of soluble CD14, by excess free LPS, or by an excess of unlabeled Gram-negative bacteria. In contrast, intact Gram-positive bacteria fail to inhibit this process. These experiments define a CD14-dependent phagocytosis pathway for Gram-negative bacteria that operates in monocytes in human whole blood. This pathway may be able to deal with bacterial pathogens that have developed resistance to complement-dependent opsonization and phagocytosis by neutrophils.
Human RANTES acts as a receptor antagonist for guinea pig eotaxin in vitro and in vivo.
Authors: Marleau S , Griffiths-Johnson D A , Collins P D , Bakhle Y S , Williams T J , Jose P J 
Published: December 2022

Abstract
The guinea pig C-C chemokine, eotaxin, is a potent and selective eosinophil chemoattractant in guinea pig airways and skin in vivo, and stimulates both guinea pig and human eosinophils in vitro. The human C-C chemokine RANTES (30% homology with guinea pig eotaxin) stimulates human eosinophils in vitro, but does not stimulate guinea pig eosinophils, even though these cells bind 125I-RANTES. Similar concentrations of eotaxin and unlabeled RANTES competitively inhibit the binding of 125I-RANTES to guinea pig eosinophils, suggesting that eotaxin and RANTES share a common binding site on these cells. In the present study, we investigated the possibility that human RANTES, binding to a putative eotaxin receptor on guinea pig eosinophils, might block functional responses to eotaxin. When fura-2-loaded cells were first exposed to RANTES, which failed to elevate the intracellular calcium concentration, the response to a subsequent challenge with eotaxin was inhibited in a dose-dependent manner. Inhibition was also demonstrated when the two chemokines were added simultaneously. Another human C-C chemokine, MCP-3 (52% homology with guinea pig eotaxin), had similar inhibitory effects on the eotaxin-induced activation of guinea pig eosinophils in vitro. RANTES inhibited (111)In-eosinophil accumulation in response to intradermal eotaxin in vivo. In contrast, RANTES had no significant effect on responses to leukotriene B4 in vitro or in vivo. Thus, these experiments in the guinea pig demonstrate that human RANTES is the first prototypic antagonist of an eotaxin receptor.
Immunomodulatory effects of IL-12 on allergic lung inflammation depend on timing of doses.
Authors: Sur S , Lam J , Bouchard P , Sigounas A , Holbert D , Metzger W J 
Published: December 2022

Abstract
We investigated the effects of IL-12 on a murine model of allergic lung inflammation. Administration of IL-12 was timed to interfere with either allergic sensitization (early dosage) or the hypersensitivity inflammatory response in the lung (late dosage), or both (early and late dosages). Comparisons of IL-12- and PBS-treated animals within each treatment group revealed several noticeable effects of IL-12. Early dosage, and the combination of early and late dosages, strikingly decreased ragweed-specific serum IgE, tracheal ring reactivity to acetylcholine, and BAL eosinophilia following allergen challenge. In contrast, late dosage had no effect on IgE levels and only a minimal effect on tracheal ring reactivity, but had a modest effect on recruitment of eosinophils. Early dosage down-regulated IL-5 and IL-10, but did not alter IL-4 or IFN-gamma expression. Late dosage down-regulated IL-5, up-regulated IL-10 and IFN-gamma, but did not change IL-4 expression. The combination of early and late dosage down-regulated IL-4, IL-5, and IL-10 expression, but increased IFN-gamma expression and production in the BAL cells and fluids. Taken together, these results indicate that IL-12 has potent immunomodulatory effects on allergic lung inflammation that depend on the timing of IL-12 administration relative to allergic sensitization and allergen challenge.
Disease-specific changes in gammadelta T cell repertoire and function in patients with pulmonary tuberculosis.
Authors: Li B , Rossman M D , Imir T , Oner-Eyuboglu A F , Lee C W , Biancaniello R , Carding S R 
Published: December 2022

Abstract
Although gammadelta T cells are known to contain the highest frequency of mycobacteria-reactive cells in humans and numerous studies have suggested that they play an important role in the initial immune response to Mycobacterium tuberculosis (Mtb), very few studies have attempted to analyze these cells in patients with active pulmonary tuberculosis. The aim of the present study was therefore to evaluate the consequences of infection on the number and activity of mycobacteria-reactive gammadelta T cells. Three-color flow cytometric analysis of blood and bronchoalveolar lavage gammadelta T cells of patients diagnosed with active pulmonary tuberculosis showed that compared with normal healthy subjects and patients with the unrelated pulmonary granulomatous diseases sarcoidosis and berylliosis the size of the mycobacteria-reactive Vgamma9+/Vdelta2+ gammadelta T cell subset in both the blood and lung was dramatically reduced. In addition, the Vgamma9+/Vdelta2+ cells left intact in patients with tuberculosis were refractory to in vitro stimulation by Mtb Ags, which are potent stimuli for these cells in normal subjects. Our results demonstrate for the first time a strong correlation between the absence or loss of the major Vgamma9+/Vdelta2+ Mtb-reactive subset of gammadelta T cells and manifestations of disease, consistent with the hypothesis that these gammadelta T cells play a role in the protective immune response to Mtb infection.
A natural IgA-anti-F(ab')2gamma autoantibody occurring in healthy individuals and kidney graft recipients recognizes an IgG1 hinge region epitope.
Authors: Terness P , Navolan D , Moroder L , Siedler F , Weyher E , Kohl I , Dufter C , Welschof M , Drugarin D , Schneider F , Opelz G 
Published: December 2022

Abstract
Natural anti-IgG autoantibodies are found both in healthy individuals and in patients with certain diseases. One group of these Abs recognizes epitopes located in the F(ab')2 region of the IgG molecule. The immunoregulatory role of these Abs in healthy individuals, graft rejection, and disease was previously studied, usually with a focus on the characterization of anti-idiotypic Abs. In the present study, we characterize the epitope recognized by an anti-F(ab')2gamma autoantibody of the IgA isotype, which occurs in the serum of healthy individuals and kidney transplant recipients. The autoantibody described herein reacts strongly with F(ab')2gamma but only poorly with Fab(gamma) fragments, a binding pattern pointing to an epitope located in the hinge region. Using synthetic peptides, we identified a conformational epitope that overlaps the middle and part of the lower hinge region. Structural analyses of peptide constructs showed that a defined conformation of the first three residues of the lower hinge is required for a full expression of the epitope. Binding of IgA to the hinge region of IgG1 covers part of the physiologically active Fc domain, immobilizes the Fab arms, and thereby can be expected to exert immunoregulatory functions.