bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective expression of integrin alpha 4 beta 7 on a subset of human CD4+ memory T cells with Hallmarks of gut-trophism.
Authors: Schweighoffer T , Tanaka Y , Tidswell M , Erle D J , Horgan K J , Luce G E , Lazarovits A I , Buck D , Shaw S 
Published: January 2023

Abstract
Human memory CD4+ T lymphocytes are heterogenous in expression of integrins; one subset has the unexpected phenotype beta 1 low alpha 4 high. We demonstrate that this subset is unique among CD4+ cells in expression of high levels of alpha 4 beta 7, detected by a distinctive mAb Act-1. alpha 4 beta 7 is involved in binding to both fibronectin and vascular cell adhesion molecule-1; Act-1 blocks cell binding to the former and augments binding to the latter. Act-1 expression marks a subset of memory cells that, unlike the predominant circulating memory cell, has up-regulated beta 7 rather than beta 1. Their phenotype is distinct from that described for skin-homing T cells and is fully consistent with that described for gut-homing T cells. Differential adhesion capacity of this subset is verified by selective binding to FN and vascular cell adhesion molecule-1 in a beta 1-independent fashion. Thus, alpha 4 beta 7 detected on this subset of circulating normal T cells fits the expectations for a gut-homing receptor.
Identification of Caucasian CD4 T cell epitopes on the circumsporozoite protein of Plasmodium vivax. T cell memory.
Authors: Bilsborough J , Carlisle M , Good M F 
Published: January 2023

Abstract
We have identified a population of Caucasians with a defined past history of infection with Plasmodium vivax malaria. Using purified synthetic peptides overlapping the sequence of the circumsporozoite protein, we determined the percentage of individuals whose T cells proliferated or secreted IFN-gamma in response to peptide stimulation, for both this population and a population of nonmalaria-exposed control individuals. A number of peptides were recognized by both groups, but 11 peptides were uniquely recognized by the exposed population, and thus represented malaria-specific T cell epitopes. CD4 T cells were found to be responsible for the proliferative response. Humans last exposed to vivax sporozoites as long ago as 49 yr responded as well or better to these malaria-specific epitopes as individuals exposed within the previous month. Since such malaria-induced memory response may not be a feature of Plasmodium falciparum infections, and since P. falciparum does not have a persisting hypnozoite stage, our data argue that the persistence of T cell memory to vivax epitopes may result from antigenic persistence in the liver.
Characterization of a (+)-azidophenazocine-sensitive sigma receptor on splenic lymphocytes.
Authors: Garza H H , Mayo S , Bowen W D , DeCosta B R , Carr D J 
Published: January 2023

Abstract
A study was undertaken to structurally define and functionally assess sigma receptors on splenocytes using the highly selective sigma ligand (+)-azidophenazocine. Radioreceptor assays under reduced lighting show (+)-azidophenazocine can effectively block the binding of sigma ligands [3H]haloperidol (IC50 = 30 nM, Ki = 19.0 nM) and [3H](+)-pentazocine (IC50 = 40 nM, Ki = 350 nM), but not the dopamine (D2) ligand [3H]spiperone (IC50 &gt; 5 microM) to splenic lymphocytes. [3H](+)-1-Propyl-3-(3-hydroxyphenyl)piperidine ([3H](+)-PPP) sites (Kd = 40.8 nM, Bmax = 2.32 pmol/mg) were also present on these lymphocytes. Additional studies using [3H](+)-azidophenazocine indicated the presence of saturable sites (Kd = 29.7 nM, Bmax = 760 fmol/mg) on splenic lymphocytes. There are no significant differences in affinity between sites found on T-enriched (Kd = 59 +/- 47 nM) and B-enriched lymphocytes (Kd = 23 +/- 5 nM). Photoaffinity labeling studies of splenocyte membranes with [3H](+)-azidophenazocine revealed a protein migrating at an apparent m.w. of 57 kDa under reducing and nonreducing conditions on SDS-PAGE. The labeling was specific because pretreatment with unlabeled haloperidol, (+)-PPP, 1,3 di(2-tolyl)guanidine, (+)-pentazocine, and (+)-azidophenazocine before cross-linking competed away &gt; 75% of the radioactivity associated with the protein, whereas (-)-pentazocine and naloxone were significantly less effective. This data together with the observation that both (+)-azidophenazocine or haloperidol inhibit Con A-induced production of IFN by splenocytes, indicates that lymphocytes possess a biologically relevant sigma receptor.
Antioxidant treatment of thymic organ cultures decreases NF-kappa B and TCF1(alpha) transcription factor activities and inhibits alpha beta T cell development.
Authors: Ivanov V , Merkenschlager M , Ceredig R 
Published: January 2023

Abstract
Using electrophoretic mobility shift assays (EMSA), we have recently shown that nuclear extracts of 14-day mouse fetal thymocytes contain abundant NF-kappa B transcription factor activity. To determine the functional role of NF-kappa B in early thymocyte development, we have exposed fetal thymus organ cultures to inhibitors of NF-kappa B activation, namely the antioxidants N-acetyl-L-cysteine and butylated hydroxyanisole. Both compounds caused a dose-dependent arrest of thymocyte differentiation toward alpha beta, but not gamma delta, T cells. This was associated with a profound decrease in nuclear content of NF-kappa B and TCF1(alpha) transcription factor activity, as determined by EMSA. In contrast, NF-Y was affected less strongly, and cyclic AMP-response-element-binding protein levels remained essentially unchanged by antioxidants. To test the idea that alpha beta T cell development is correlated with NF-kappa B and TCF1(alpha) activity, we conducted additional experiments in a submersion culture system in which the generation of alpha beta T cells can be manipulated. Standard submersion culture supports gamma delta but alpha beta T cell development. Under these conditions, EMSA showed that transcription factor activities were similar to those seen in the presence of antioxidants. Importantly, when the generation of alpha beta T cells in submersion culture was restored by elevating oxygen concentrations, there was a dramatic increase in TCF1(alpha) activity, and both NF-kappa B and NF-Y returned to control levels. Taken together, these results strongly suggest that NF-kappa B and TCF1(alpha), presumably in concert with other transcription factors, play an important role in the development of alpha beta T cells.
Spontaneous and IL-2-induced anti-leukemic and anti-host effects against tumor- and host-specific alloantigens.
Authors: Cohen P , Vourka-Karussis U , Weiss L , Slavin S 
Published: January 2023

Abstract
The graft-vs-leukemia (GVL) effect and its connection to graft-vs-host disease (GVHD) were studied in F1 hybrid mice after parental bone marrow transplantation. (BALB/c x C57BL/6) F1 mice (F1) were sublethally and lethally irradiated and inoculated with 10(4) BCL1 cells, a murine leukemia of BALB/c (BALB) origin. Subsequently mice were transplanted with F1 (syngeneic), BALB (allogeneic to the host but syngeneic to the tumor), C57BL/6 (B6) (allogeneic to both host and tumor) spleen cells, or spleen cells mixed with syngeneic (F1) bone marrow cells, respectively. Fresh BALB (H-2d) and B6 (H-2b) spleen cells, which induce equally strong GVHD in the F1 recipient against H-2b and H-2d alloantigens, respectively, were assayed for their ability to induce GVL effects on BCL1 (H-2d) cells with and without in vivo administration of human rIL-2. In order to increase the GVL effects, spleen cells were incubated for 4 days with rIL-2 to generate IL-2-activated killer cells. The results of adoptive transfer experiments showed that only immunocompetent B6 cells led to consistent eradication of leukemia. Neither BALB nor syngeneic F1 cells induced curative GVL effects regardless of whether spleen cells were further stimulated with rIL-2 in vitro, in vivo, or both. Our data support the theory that GVL effects are caused by T cell-dependent immune responses of allogeneic T cells and not by MHC-nonrestricted NK or rIL-2-activated NK cells, independently of the GVHD process itself. Hence, recognition and killing of tumor cells is most probably a MHC-restricted T cell-dependent process.
Regulation of adhesion of CD4+ T lymphocytes to intact or heparinase-treated subendothelial extracellular matrix by diffusible or anchored RANTES and MIP-1 beta.
Authors: Gilat D , Hershkoviz R , Mekori Y A , Vlodavsky I , Lider O 
Published: January 2023

Abstract
Chemokines, a superfamily of 8- to 11-kDa mediators of inflammation, affect the attachment of immune cells to vascular endothelia by binding to cell surface glycosaminoglycans. We analyzed whether chemokines are also involved in interactions between CD4+ T lymphocytes and the subendothelial extracellular matrix (ECM). Soluble mediators, such as MIP-1 beta and RANTES, induced the binding of resting human CD4+ T cells to ECM in an integrin-dependent manner. Both MIP-1 beta and RANTES bound to intact ECM and retained their adhesive properties, and moreover, ECM-bound RANTES and MIP-1 beta prolonged the time course of interactions between the CD4+ T cells and the ECM. Because the adhesive effect of these chemokines was restricted by an inhibitor of GTP-binding proteins, the adhesive effect of ECM-bound RANTES and MIP-1 beta, which requires an intact cytoskeleton, seems to involve activation of a G protein-linked receptor. MIP-1 beta and RANTES exert their pro-adhesive effects through interactions with glycosaminoglycans, because heparinase-treated ECM did not bound chemokines and because the chemokines ability to induce T cell adhesion was abrogated if: 1) either of the chemokines is pretreaed with heparin or heparan-sulfate (HS), 2) HS is removed from intact ECM by heparinase, an HS-specific endoglycosidase, or 3) the ECM-bound chemokines are released by pretreatment with heparinase. Hence, the adhesive effects of immobilized chemokines is not restricted to T cells interacting with endothelial cells, but also affects the migration of immune cells which reside and function in the context of ECM.
Cross-linking of CD53 promotes activation of resting human B lymphocytes.
Authors: Rasmussen A M , Blomhoff H K , Stokke T , Horejsi V , Smeland E B 
Published: January 2023

Abstract
The CD53 pan-leukocyte glycoprotein is a member of the recently described tetraspan family of cell membrane proteins. The structure and functional characteristics of these molecules indicate that they may play important roles in transmembrane signaling in different cells. Recently, it was reported that cross-linking of CD53 on human B cells led to an increase in cytoplasmic calcium fluxes. In the present study, we wished to further explore the possible role of CD53 in functional B cell responses. Cross-linking of CD53 with the use of the mAb MEM-53 and a polyclonal sheep anti-mouse Ig promoted activation of resting B cells into the G1 phase of the cell cycle as judged by increased expression of the early activation Ag CD69, increases in cellular volume, RNA synthesis, and c-myc protein levels, and enhanced binding of 7-aminoactinomycin D. In contrast, MEM-53 alone had no detectable effects. Cross-linking of anti-CD53 induced negligible S phase entry in the absence of other stimuli. However, cytokines, in particular IL-2 and IL-4, potentiated the DNA synthesis induced by cross-linking of CD53. Furthermore, cross-linking of the CD53 Ag induced Ig production in the presence of T cell supernatant. Taken together, the data suggest that CD53 plays an important functional role in B cell activation and differentiation.
Differential transcriptional activities of HLA-DR genes in the various haplotypes.
Authors: Louis P , Vincent R , Cavadore P , Clot J , Eliaou J F 
Published: January 2023

Abstract
The regulation of HLA class II genes is of particular interest with regard to the modulation of the immune response. The polymorphism of their coding regions is directly involved in the specificity of the Ag presentation, and their level of expression affects the extent of T cell activation. Previously, we have described an allelic polymorphism in the proximal promoter regions of HLA-DRB genes. The aim of this study was to compare the transcriptional activities of the promoters of the DRB genes and DRB1 alleles in a transient expression system. We have demonstrated a marked difference in their promoter strengths, as determined by their relative abilities to initiate transcription of the chloramphenicol acetyltransferase reporter gene in human B cell lines. The polymorphism of the promoter regions has been mapped to the regulatory boxes, and, by using gel retardation experiments, we found a differential ability of the nuclear proteins to bind to the partially conserved X box regions. Taken together, our results demonstrate the functional consequences of the allelic polymorphism of the proximal promoter regions of the DRB genes. These findings strongly suggest the existence, for the HLA-DR genes, of an interdependence between the polymorphism of the coding regions, which directly affects the capacity of peptide binding, and the polymorphism of the regulatory regions, which influences the transcriptional activities of the promoters.
Two forms of the mb-1 gene transcript in cattle.
Authors: Youn H Y , Goitsuka R , Okuda M , Watari T , Tsujimoto H , Hasegawa A 
Published: January 2023

Abstract
We have isolated two forms of bovine mb-1 cDNA clones from a cDNA library of a bovine leukemia virus-infected B-lymphoblastoid cell line. The nucleotide sequence analysis of these cDNA clones indicated that the shorter form of cDNA had a 119-bp deletion that precisely corresponded to the exon III domain of the human and murine mb-1 genes. This deletion would result in a frame shift, producing a premature translation termination leading to the lack of the entire transmembrane and cytoplasmic domains of the normal mb-1 molecule. The existence of two species of mRNA transcripts corresponding to the isolated cDNA clones were confirmed in all of the bovine leukemia cell lines examined by PCR with the use of the primers flanking the deletion site. Furthermore, the shorter mb-1 transcript was induced in normal PBMC by stimulation with mitogens or culture supernatants of bovine leukemia virus-infected cell lines. These findings indicate the presence of the truncated mb-1 gene product which may have some function different from that of the normal mb-1 gene product.
Elevated expression of Th1 cytokines and nitric oxide synthase in the lungs of vaccinated mice after challenge infection with Schistosoma mansoni.
Authors: Wynn T A , Oswald I P , Eltoum I A , Caspar P , Lowenstein C J , Lewis F A , James S L , Sher A 
Published: January 2023

Abstract
C57BL/6 mice were vaccinated with irradiated cercariae of Schistosoma mansoni, and, at various times after challenge infection, total lung mRNA was isolated to assess the induction of several cytokines that previously had been shown in in vitro studies to be involved in the activation of macrophages and/or endothelial cells for nitric oxide (NO) production and killing of schistosomula. Vaccinated mice demonstrated a highly significant increase in IFN-gamma mRNA upon subsequent infection when compared with infected nonvaccinated controls. A similar, although less dramatic, increase in two other macrophage-activating cytokines, TNF-alpha and IL-2, also was observed. In contrast, although the Th2 cytokines IL-4, IL-5, IL-10, and IL-13 were elevated in challenged vaccinated animals, only IL-10 and IL-13 showed increases that were significant with respect to the mRNA levels observed in challenged controls. Neutralization of IFN-gamma reduced immunity in vaccinated animals and resulted in decreased IFN-gamma, IL-2, IL-10, TNF-alpha, and IL-12 p40 but markedly increased IL-4, IL-5, and IL-13 mRNA expression and serum IgE levels. Pulmonary NO synthase expression was elevated in immunized mice at a time at which immune elimination of schistosomula is believed to occur. Moreover, suppression of NO synthase activity with the inhibitor aminoguanidine reduced immunity, as measured by a 32 to 33% increase in worm burden. Together, these data support previous in vitro studies that suggest a role for NO in schistosomulum killing. Furthermore, the observation that the down-regulatory cytokines IL-4, IL-10, and IL-13 are induced together with IFN-gamma may provide an explanation for the failure of this vaccine to provide complete protection.
Tolerance to a self-peptide from the third hypervariable region of HLA DRB1*0401 in rheumatoid arthritis patients and normal subjects.
Authors: Salvat S , Auger I , Rochelle L , Begovich A , Geburher L , Sette A , Roudier J 
Published: January 2023

Abstract
The third hypervariable region (HV3) of HLA-DRB1*0401 helps the development of severe rheumatoid arthritis by an unknown mechanism. To test whether the third hypervariable region of HLA-DRB1*0401 may shape the T cell repertoire, we studied proliferative responses to peptides encompassing the third hypervariable region of seven HLA-DRB1 alleles in normal subjects and patients with rheumatoid arthritis. We found that, in general, there is no tolerance to peptides from the third hypervariable region of self-HLA-DRB1 alleles. However, a peptide from the third hypervariable region of DRB1*0401 (DRB1*0401 HV3 peptide) is tolerated in people who express HLA-DRB1*0401. Indeed, PBMCs from people who express DRB1*0401 do not proliferate to DRB1*0401 HV3 peptide. Conversely, people who express DRB1*1501 respond to DRB1*0401 HV3 peptide. Finally, people who express both DRB1*0401 (nonresponder haplotype) and DRB1*1501 (high responder haplotype) do not respond to DRB1 HV3 peptide, thus demonstrating tolerance. Therefore, the third hypervariable region of HLA-DRB1*0401 shapes the T cell repertoire.
Activation-induced cell death in proliferating T cells is associated with altered tyrosine phosphorylation of TCR/CD3 subunits.
Authors: Orchansky P L , Teh H S 
Published: January 2023

Abstract
The first signaling event that occurs after stimulation of the TCR is an increase in the tyrosine phosphorylation of a number of proteins including the TCR-zeta chain and CD3 subunits. It is known that proliferating T cells respond differently to TCR stimulation when compared with naive T cells. Stimulation of the TCR on proliferating T cells has been shown to result in cell death by apoptosis, a process referred to as activation-induced cell death (AICD). In this study we have determined the pattern of tyrosine phosphorylation of TCR-zeta and the CD3 subunits of naive and proliferating CD4- CD8+ T cells that express a transgenic TCR that is specific for the male Ag presented by Db class I molecules after TCR stimulation. AICD in proliferating T cells was mediated by stimulation with anti-TCR/CD3, but not anti-Thy-1, anti-CD8, or anti-Db mAbs. When compared with naive T cells, tyrosine phosphorylation of TCR-zeta was dramatically decreased in proliferating cells. Furthermore, whereas CD3 delta, CD3 epsilon, and CD3 gamma of naive T cells were phosphorylated in a 1:2:1 ratio after TCR stimulation, these subunits in proliferating T cells were tyrosine phosphorylated in a 1:1:0 ratio after TCR stimulation. Altered phosphorylation of these subunits was not caused by the lack of synthesis or amount of these proteins in proliferating cells. This is the first study implicating altered tyrosine phosphorylation of TCR/CD3 subunits in AICD.
Production of IgE antibody and allergic sensitization of intestinal and peripheral tissues after oral immunization with protein Ag and cholera toxin.
Authors: Snider D P , Marshall J S , Perdue M H , Liang H 
Published: January 2023

Abstract
Cholera toxin (CTX) is a potent oral adjuvant for the induction of mucosal IgA Ab responses protein Ags. We examined the Ab responses and allergic sensitization of several strains of mice to protein Ags, administered orally with CTX. The mice made strong IgA and IgG1 serum Ab responses, but little IgG2a Ab to Ags such as hen egg lysozyme (HEL) and OVA. However, when given a subsequent i.p. challenge with Ag alone, the same mice had immediate hypersensitivity reactions that included respiratory distress and death. Within 10 min of i.p. challenge, immunized mice had high levels of plasma histamine and extensive degranulation of mast cells in target tissues. These mice had detectable serum IgE Ab. Ag administered orally with the B subunit (CTB) of CTX did not sensitize mice. Intestinal tissues taken from these mice had Ag-specific ion-secretory responses in vitro, typical of intestinal anaphylaxis. Ag given s.c. without adjuvant could also sensitize for systemic and intestinal anaphylaxis. Sensitization with HEL given s.c. was dose dependent and correlated with a critical amount of HEL in the circulation. HEL was detected in the circulation after oral immunization, but CTX did not increase the uptake of HEL. Thus, oral immunization with a protein Ag in the presence of CTX can sensitize an animal for systemic and intestinal anaphylaxis. These results suggest a cautious approach to the use of CTX as an adjuvant in oral vaccines, and provide a new model to study immediate hypersensitivity reactions to intestinal Ag.
Secretory vesicles are the intracellular reservoir of complement receptor 1 in human neutrophils.
Authors: Sengeløv H , Kjeldsen L , Kroeze W , Berger M , Borregaard N 
Published: January 2023

Abstract
The subcellular localization of complement receptor 1 (CR1) was investigated in human neutrophils. CR1 was located exclusively in the light membrane fractions containing secretory vesicles and plasma membranes in Percoll density gradients of unperturbed neutrophils. Separation of plasma membranes from secretory vesicles by high-voltage free-flow electrophoresis of the light membranes from the Percoll gradient revealed that more than 80% of the CR1 was located intracellularly in secretory vesicles. After weak stimulation of neutrophils, the increase in CR1 surface expression closely paralleled both surface increase of known secretory vesicle membrane Ags and the release of matrix proteins from secretory vesicles. More potent stimulation of the neutrophils did not enhance CR1 surface expression further, in agreement with the lack of CR1 in granules as demonstrated on Percoll gradient. CR3 (Mac-1), which has been shown to be located both in secretory vesicles and in neutrophil granules, was up-regulated in parallel with CR1 after weak stimuli, whereas a profound increase of CR3 was observed after more potent stimuli in accordance with granule mobilization. These results identify secretory vesicles as the reservoir of CR1, which translocates to the plasma membrane after weak stimulation, and underscore the functional significance of this recently identified organelle.
Immune-mediated brain atrophy. CD8+ T cells contribute to tissue destruction during borna disease.
Authors: Bilzer T , Stitz L 
Published: January 2023

Abstract
Borna disease (BD) is a virus-induced immunopathologic disease of the central nervous system in a variety of species from birds to primates and probably in humans. Severe inflammatory reactions lead to tissue destruction and finally to cortical brain atrophy. After experimental infection of the rat, intraparenchymal CD8+ T cells, MHC class I Ags on Borna disease virus (BDV)-infected neurons, and numerous nerve cell lesions were present. Treatment of BDV-infected rats with the mAb OX-8 directed against CD8+ cells inhibited the immunopathologic reactions and reduced MHC class I Ag expression. Neuronal lesions were minimal and no loss of brain substance could be observed. Because BDV has no acute cytopathic effects, we provide evidence that the presence of CD8+ T cells within the brain parenchyma and the expression of MHC class I Ags on neurons play a major role for immunopathologic brain tissue destruction and virus-infected neurons in vivo can be destroyed by T cell-mediated cytotoxicity.