bluuebunny/crossref_metadata_2025_split huggingface dataset:
The main IgE-binding epitope of a major latex allergen, prohevein, is present in its N-terminal 43-amino acid fragment, hevein.
Authors: Alenius H , Kalkkinen N , Reunala T , Turjanmaa K , Palosuo T 
Published: December 2022

Abstract
Polypeptides of natural rubber latex (NRL) that elute from surgeon's gloves and other manufactured rubber products can sensitize exposed individuals and elicit severe hypersensitivity reactions. Previously, we showed that prohevein is a major allergen in NRL, the source material for rubber manufacturing. To analyze which region of the molecule carries the main IgE-binding epitope(s), we purified prohevein and its C-domain from NRL by gel filtration, reverse phase chromatography, and electroelution. In immunoblotting, prohevein bound IgE from 15 of 20 (75%), and the prohevein C-domain from 3 of 20 (15%) latex-allergic patient sera. In ELISA, 36 of 52 (69%) patient sera showed IgE binding to prohevein, whereas 11 of 52 (21%) sera had IgE to prohevein C-domain. We then purified from a brand of highly allergenic surgeon's gloves six hydrophilic peptides that revealed in amino-terminal sequencing 100% identity to the N-terminus of prohevein. In mass spectrometry, all purified peptides gave a molecular mass of 4719 +/- 1.9 daltons, which corresponds to the molecular mass of hevein (4719.1 daltons), a 43-amino acid N-terminal fragment of prohevein. Purified hevein inhibited 72% of IgE binding from pooled sera of NRL-allergic patients to solid phase glove extract and 45% of IgE binding to solid phase NRL. Of the 43 NRL-allergic patient sera tested, 56% showed IgE Abs to purified hevein in ELISA. In skin prick testing, purified hevein elicited positive reactions in three-quarters of the latex-allergic patients tested. These results indicate that the majority of prohevein's IgE-binding ability resides in its N-terminal fragment, known as hevein. In one highly allergenic latex glove examined, the majority of IgE-binding ability was attributable to hevein molecules, suggesting that these peptides can be significant sensitizers in NRL allergy.
HIV-1-Tat modulates the function of monocytes and alters their interactions with microvessel endothelial cells. A mechanism of HIV pathogenesis.
Authors: Lafrenie R M , Wahl L M , Epstein J S , Hewlett I K , Yamada K M , Dhawan S 
Published: December 2022

Abstract
Monocytes are major targets of HIV infection in patients with AIDS. In vitro infection of monocytes with HIV is associated with increased expression of beta 2 integrins, which increases both monocyte aggregation and monocyte/endothelial adhesion as well as monocyte metalloproteinase (MMP-9) expression. Treatment of primary monocytes with soluble HIV-Tat protein mimicked many of the properties of HIV infection of monocytes. Tat treatment up-regulated the expression of the beta 2 integrins, which was associated with the formation of large aggregates of monocytes and increased adhesion to endothelial monolayers. Treatment of monocytes with Tat increased their adhesion to both untreated and TNF-alpha-treated endothelial monolayers, and adhesion was inhibited by inclusion of anti-beta 2 and anti-ICAM-1 Abs. The increased adhesion of activated monocytes was accompanied by substantial disruption of the endothelial monolayers, with retraction or detachment of individual endothelial cells. Tat treatment of monocytes up-regulated the synthesis and release of the protease MMP-9, providing a potential mechanism to explain endothelial cell/basement membrane detachment. Thus, extracellular Tat is capable of activating monocytes even in the absence of HIV infection. Our studies demonstrate that many of the effects of HIV infection on monocyte homotypic and heterotypic adhesion, protease secretion, and disruption of the endothelium can be mimicked by treatment with HIV-Tat protein alone. These results suggest a mechanism where monocytes could be inappropriately activated by HIV-Tat, secreted by HIV-infected cells, causing them to extravasate into underlying tissues and ultimately contribute to tissue damage as seen during the progression of AIDS.
Serum high molecular weight dipeptidyl peptidase IV (CD26) is similar to a novel antigen DPPT-L released from activated T cells.
Authors: Duke-Cohan J S , Morimoto C , Rocker J A , Schlossman S F 
Published: December 2022

Abstract
This study demonstrates that the 175-kDa form of dipeptidyl peptidase IV (DPPIV) found in normal human serum is identical with a similarly-sized Ag, DPPT-L, found to be rapidly expressed on the surface of activated T cells. As activation progresses, the expression of DPPT-L reaches a peak on day 3, after which expression falls, whereas expression of the 105-kDa CD26/DPPIV detected by the mAb 1F7 increases, as does the ability to bind adenosine deaminase. The loss of DPPT-L from the surface of activated T cells correlates exactly with the appearance of DPPT-L and DPPIV activity in serum-free tissue culture medium. The release of DPPIV was generally greater from CD4+ cells than from CD8+ T cells, and within the CD4+ subset, the CD45RO+ subset was the major source, which correlated with surface expression before culture. We show that the DPPIV released from activated T cells is antigenically, biochemically, and enzymatically similar to DPPIV circulating in the serum and is distinct from the DPPIV activity of 105-kDa CD26. The T cell-released DPPIV is able to function as a costimulating molecule for the response to the recall Ag, tetanus toxoid, at levels similar to those at which recombinant soluble CD26 and serum DPPIV exhibit costimulatory function, suggesting that the released DPPIV may serve an important immunoregulatory function in vivo, both locally and within the systemic circulation.
Biochemical characterization of antigen-specific glycosylation-inhibiting factor from antigen-specific suppressor T cells. I. Identification of a 55-kilodalton glycosylation-inhibiting factor peptide with TCR alpha-chain determinant.
Authors: Nakano T , Ishii Y , Ishizaka K 
Published: December 2022

Abstract
Stimulation of OVA-specific suppressor T cell (Ts) hybridoma and bee venom phospholipase A2 (PLA2)-specific Ts hybridoma with Ag-pulsed APC or by cross-linking of CD3 resulted in the formation of Ag-specific glycosylation-inhibiting factor (GIF). Affinity-purified Ag-specific GIF preparations, obtained by using Ag-coupled Sepharose or anti-TCR alpha-chain-coupled Affi-Gel, contained a 55-kDa peptide, which bound both polyclonal anti-GIF Abs and anti-TCR-alpha mAb in immunoblotting. The same hybridomas constitutively secrete 13-kDa bioactive GIF peptide that has no affinity for homologous Ag, but neither the Ag-specific GIF activity nor 55-kDa GIF peptide was detectable in culture supernatants of unstimulated cells. Northern blot analysis of mRNA from the anti-CD3-stimulated hybridoma with 32P-labeled GIF cDNA revealed only 0.6 kb mRNA, which encodes the 13-kDa nonspecific GIF. No mRNA of the 55-kDa GIF was detectable. A representative OVA-specific Th hybridoma, DO 11.10 cells contain the 0.6 kb GIF mRNA and constitutively secrete inactive GIF peptide. However, the Th hybridoma failed to secrete the 55-kDa peptide or any peptide with the TCR-alpha determinant upon stimulation with anti-CD3. It appears that the formation of the 55-kDa peptide with the TCR-alpha determinant is unique for a subset of T cells including Ts cells that form bioactive GIF.
Cells treated with TAP-2 antisense oligonucleotides are potent antigen-presenting cells in vitro and in vivo.
Authors: Nair S K , Snyder D , Gilboa E 
Published: December 2022

Abstract
Treatment of RMA and EL4 cells or freshly isolated splenocytes with antisense (AS) oligonucleotides directed against the TAP-2 gene recreates the phenotype seen in cells that are genetically deficient in TAP function. Cells incubated with AS oligonucleotides exhibit reduced MHC class I expression on the cell surface, which can be increased by incubating the oligonucleotide-treated cells at 28 degrees C or by adding MHC haplotype-matched peptides to the culture medium. RMA cells or splenocytes treated with AS oligonucleotides and incubated with peptide were highly effective in generating primary CTL responses in vitro. The bulk of the AS oligonucleotide-responsive and CTL-inducing cells resided in the adherent fraction of splenocytes. Moreover, TAP-2 AS oligonucleotide-treated adherent splenocytes pulsed with OVA peptide elicited potent OVA-specific CTL responses in vivo and provided effective protection from challenge with tumor cells expressing the corresponding Ag. AS oligonucleotide technology provides a simple approach to develop broadly applicable methods for generating potent APC to study TAP function in normal cells and to identify other gene products involved in MHC class I presentation.
Human IL-13 production is negatively influenced by CD3 engagement. Enhancement of IL-13 production by cyclosporin A.
Authors: van der Pouw Kraan T C , Boeije L C , Troon J T , Rutschmann S K , Wijdenes J , Aarden L A 
Published: December 2022

Abstract
IL-13, a T cell-derived cytokine, shares many of its biologic activities with the Th2 cytokine IL-4, including induction of a class switch to IgE and anti-inflammatory properties. Its potential impact on development of Th2 responses makes it interesting to determine how the production of IL-13 is regulated and which cell types produce IL-13. In this work, we show that IL-13 is produced optimally by T cells when stimulated with a combination of anti-CD28 and PMA. Unexpectedly, additional ligation of the TCR complex with Abs to CD3 caused an approximately fivefold inhibition of IL-13 production. Moreover, this inhibition could be reversed by cyclosporin A (CsA). The effect of CsA did not depend on the presence of PMA; upon CD3 and CD28 stimulation, CsA equally enhanced IL-13 production. Both naive and memory CD4+ T cells and CD8+ T cells produced IL-13, and production in all cell types could be enhanced by CsA. In contrast to IL-13, IL-4 production was observed mainly in CD4+ memory cells, required costimulation through CD3, and was inhibited by CsA. The unusual regulation and relative abundance of IL-13 make it an important candidate to be controlled tightly by dose and type of TCR ligands. CsA is used widely to inhibit T cell function. The finding that IL-13 production is enhanced instead of diminished in the presence of CsA may explain the Th2-inducing effects of CsA in vivo.
TCRV beta 7+ Th2 cells mediate UVB-induced suppression of murine contact photosensitivity by releasing IL-10.
Authors: Yagi H , Tokura Y , Wakita H , Furukawa F , Takigawa M 
Published: December 2022

Abstract
In murine contact photosensitivity, a cutaneous delayed-type hypersensitivity reaction, preirradiation of the photosensitization site with UVB induced Ag-specific, afferent limb-acting, CD4+CD8- suppressor T cells (Ts). The present study examined usage of TCR V beta and production of immunosuppressive cytokines in Ts propagated in vitro. Spleen cells from UVB-preirradiated, 3,3',4',5- tetracholorosalicylanilide (TCSA)-photosensitized mice were stimulated with 3000-rad-irradiated lymph node cells (LNC) from TCSA/UVA-sensitized mice (LNCTCSA) in the presence of rIL-t. After several rounds of antigenic stimulation, a T cell line (B+TCL) consisted exclusively of CD3+CD4+CD8- V beta 7+ and V beta 13+ populations. Transfer to naive recipients of B+TCL treated with anti-V beta mAb plus complement revealed that the V beta 7+ cells suppressed both the in vivo and the in vitro aspects of contact photosensitivity to TCSA in an Ag-specific manner. The in vitro suppressive activity of B+TCL was neutralized by anti-IL-10 mAb, but not by anti-IL-4 mAb, indicating a crucial role of IL-10 in UBV-induced suppression. Upon stimulation with 3000-rad-irradiated-LNCTCSA, B+TCL released IL-4 and IL-10 but not IL-2, and V beta 7+ cells produced IL-10. The reverse transcriptase-PCR detected mRNA for IL-4 and IL-10 but not that for IL-2, IFN-gamma, or TGF-beta in B+TCL stimulated with or without concanavalin A. In accordance with the findings in B+TCL, spleen cells from UVB preirradiation plus TCSA/UVA mice contained V beta 7+ T cells that suppressed contact photosensitivity to TCSA and produced substantial amounts of IL-4 that provided a microenvironment for Th2 cell generation. We conclude that UVB preirradiation and photosensitization result in the generation of V beta 7+ Th2 cells that suppress contact photosensitivity by releasing IL-10. The dysfunction of effector Th1 cells underlying UVB suppression of delayed-type hypersensitivity seems to be due not only to altered APC function but also to counteraction of Th2 cells by Th1 cells.
Costimulation of fibronectin receptor promotes Fc gamma R-mediated rescue of IL-3-dependent bone marrow-derived cells from apoptosis.
Authors: Yoshikawa H , Sakihama T , Nakajima Y , Tasaka K 
Published: December 2022

Abstract
The IL-3-dependent murine bone marrow-derived cell line FDC-P2/185-4 (185-4) undergoes apoptosis when IL-3 is withdrawn from the culture medium. However, a high concentration of aggregated mouse IgG prevents apoptosis of 185-4 cells by an autocrine mechanism, producing IL-3. An analysis of flow cytometry revealed that 185-4 cells expressed Fc gamma RIII on their surface and that these effects of IgG are inhibited by anti-Fc gamma RIII mAb. These results indicated that the effect of IgG is mediated by low affinity Fc gamma RIII. In contrast, a low concentration of mouse IgG cannot prevent the apoptosis of 185-4 cells, but in the presence of fibronectin (FN), cell survival is prolonged. It is generally accepted that the interaction of cells with FN is mediated by several integrins such as alpha 5 beta 1 (VLA-5) or alpha 4 beta 1 (VLA-4), and analysis of flow cytometry showed that 185-4 cells express these integrins on their surface. Furthermore, these effects of FN are blocked specifically by RGD peptide or anti-VLA-4 mAb. These findings indicated that FN induces the costimulatory signal through integrin receptor and enhances the proliferative effect through Fc gamma RIII by a low concentration of IgG. The findings presented here suggested that the engagement of FN-integrin receptors on 185-4 cells increases the sensitivity of the cells for cellular activation of IgG. Since inflammatory cells in the microenvironment are surrounded by extracellular matrix proteins, it is possible that adhesion molecules play important roles in inflammatory states such as autoimmune diseases caused by increased levels of IgG.
A mannose 6-phosphate-containing N-linked glycopeptide derived from lysosomal acid lipase is bound to MHC class II in B lymphoblastoid cell lines.
Authors: Dustin M L , McCourt D W , Kornfeld S 
Published: December 2022

Abstract
Binding of peptides to MHC class II Ag generates ligands for TCR of Th lymphocytes. We have identified a novel class of peptides bound to MHC class II: mannose 6- phosphate (Man-6-P) containing glycopeptides from lysosomal enzymes. These species were identified in the process of characterizing mannose 6-phosphate/insulin-like growth factor II (M-6-P/IGF-II) receptor binding to the surface of B lymphoblasts. Surface iodination and Man-6-P/IGF-II receptor affinity chromatography implicated MHC class II as a carrier of Man-6-P-modified oligosaccharides. These oligosaccharides were found to be primarily associated with the bound peptide. Peptides eluted from the Man-6-P/IGF-II receptor-binding fraction of immunoaffinity-purified MHC class II from the Swei cell line contained a sequence derived from the propiece of lysosomal acid lipase. Partial sequences were also obtained for peptides from other HLA-DR alleles but none of these were attributable to known proteins. This study defines a novel approach for isolating rare glycan-modified peptides from MHC class II and demonstrates that very large secondary modifications are tolerated in peptides bound to MHC class II.
Interference between human herpesvirus 7 and HIV-1 in mononuclear phagocytes.
Authors: Crowley R W , Secchiero P , Zella D , Cara A , Gallo R C , Lusso P 
Published: December 2022

Abstract
Human herpesvirus 7 (HHV-7) uses CD4 as a cellular membrane receptor and thereby interferes with infection of CD4+ T cells by HIV-1. We studied the interactions between HHV-7 and a macrophage-tropic HIV-1 isolate (HIV-1BaL) in terminally differentiated human peripheral blood monocyte-derived macrophages, another critical target for infection by HIV-1 in vivo. Exposure of macrophages to HHV-7 alone yielded no signs of virus replication or cytopathic effects. Nevertheless, when macrophages were pre-exposed to either live or UV-inactivated HHV-7 and subsequently infected with HIV-1BaL, a significant dose-dependent inhibition of HIV-1 replication was documented. At day 7 postinfection, the average level of HIV-1 p24 Ag in cultures from five different donors was reduced by 91.7 +/- 8.3% by pretreatment with live HHV-7 and by 91.8 +/- 8.2% by pretreatment with UV-inactivated HHV-7. Moreover, the synthesis of HIV-1 proviral DNA in macrophages pretreated with HHV-7 was completely inhibited during the early stages after infection, suggesting that HHV-7 blocks HIV-1 at the level of interaction with the CD4 receptor. Consistent with this concept, both macrophage and CD4+ T cell cultures with pre-established HIV-1 infection were not susceptible to inhibitory effects of HHV-7. The proliferative response of PBMC to mitogens was only marginally inhibited by exposure to HHV-7 before mitogen stimulation, indicating that the inhibition of HIV-1 infection was not due to a negative effect on cell proliferation. These data demonstrate that HHV-7 is a powerful inhibitor of HIV-1 infection in cells of the mononuclear phagocytic lineage, despite its inability to replicate actively in such cells.
Vitamin A down-regulation of IFN-gamma synthesis in cloned mouse Th1 lymphocytes depends on the CD28 costimulatory pathway.
Authors: Cantorna M T , Nashold F E , Chun T Y , Hayes C E 
Published: December 2022

Abstract
Some infections deplete serum retinol, low retinol reduces immunity, and reduced immunity establishes susceptibility to further infection in a cyclical relationship that is poorly understood. We showed that when retinol was low, there was excessive Th1 cell IFN-gamma synthesis and inadequate Th2 cell IL-4 and IL-5 synthesis. The retinol metabolite retinoic acid inhibited the IFN-gamma stimulatory activity of APCs, enhanced Th2 cell differentiation, and inhibited Th1 cell IFN-gamma synthesis. Here we focus on the mechanism for retinoic acid inhibition of IFN-gamma synthesis in myelin basic protein-specific MM4 Th1 cells. Physiologic amounts of all-trans-retinoic acid directly and specifically down-regulated the MM4 Th1 cell IFN-gamma secretion rate in vitro without affecting cell growth, viability, or overall protein synthesis. All-trans-, 9-cis-, and 13-cis-retinoic acid, and the synthetic retinoid Ch55, inhibited IFN-gamma synthesis effectively, whereas retinaldehyde, retinol, and retinyl acetate did not. This pattern suggests retinoic acid receptor involvement in the inhibition mechanism. Retinoic acid did not inhibit when Th1 cells were activated only through the TCR/CD3 complex, with or without IL-2 costimulation. Retinoic acid inhibited IFN-gamma synthesis when the CD28 costimulatory pathway was activated in addition to the TCR/CD3 pathway, suggesting it blocks some step in the CD28 pathway. Retinoid probably acted to decrease IFN-gamma transcript accumulation by decreasing transcription because it did not decrease transcript stability. We suggest that unrestrained IFN-gamma synthesis is one key immunobiologic mechanism that accounts for poor antibody-mediated immunity in hypovitaminosis A, since IFN-gamma in relatively small amounts can limit Th2 cell growth and interfere with the B cell stimulatory functions of Th2 cell cytokines.
CD45 ligation induces programmed cell death in T and B lymphocytes.
Authors: Klaus S J , Sidorenko S P , Clark E A 
Published: December 2022

Abstract
Studies have shown an essential role for the CD45 protein tyrosine phosphatase in regulating Ag receptor-derived signals in lymphocytes. Co-ligating CD45 with the Ag receptor, however, can also inhibit receptor signaling, as manifest in T cells by the lack of IL-2 production and proliferation. We report that CD45 ligation alone induces apoptosis in normal T cells, and that death was greatly potentiated by cross-linking CD3. Normal B cells and T and B cell lines were also induced to die with insoluble CD45 mAb. CD45-induced cell death was blocked by inhibitors of protein tyrosine kinases and protein tyrosine phosphatases, but not by inhibitors of RNA or protein synthesis or by cyclosporin A. Morphologically, CD45-mediated apoptosis resembled death induced via CD95 (Fas), as evidenced by nuclear condensation and membrane blebbing, but did not cause DNA fragmentation into oligonucleosomes. Co-ligating CD45 and CD95 either enhanced or inhibited CD45-induced cell death, depending on the degree of CD45 and CD95 cross-linking. Finally, CD45 cross-linking induced its rapid association with the detergent-insoluble cell fraction, suggesting that it becomes linked to the cytoskeleton during CD45-induced apoptosis. These data show a novel role for CD45 in regulating lymphocyte death as well as proliferation.
Regulation of 3' IgH enhancers by a common set of factors, including kappa B-binding proteins.
Authors: Michaelson J S , Singh M , Snapper C M , Sha W C , Baltimore D , Birshtein B K 
Published: December 2022

Abstract
Targeted disruption of the p50 subunit of NF-kappa B resulted in isotype class switch defects resembling those observed in mice in which the downstream IgH enhancer 3'alpha E(hs1,2) was deleted. We postulated that kappa B binding proteins may regulate class switching by interacting with 3'alpha E(hs1,2) or with other IgH 3' enhancers with which 3'alpha E(hs1,2) synergizes. kappa B binding sites were identified in 3'alpha E(hs1,2) and 3' alpha-hs4, the distal 3' IgH enhancer. A kappa B binding site within 3'alpha E(hs1,2) contributes to at least half the activity of the enhancer in plasma cells, while the same kappa B binding site participates in the complex repression of the enhancer in B cells. In the case of 3'alpha-hs4, a kappa B binding complex activates the enhancer in pre-B, B cells and plasma cells. Additional binding sites within 3'alpha-hs4 for factors known to regulate 3'alpha E(hs1,2), including Oct-1 and BSAP, were identified, and their contribution to 3'alpha-hs4 regulation during B cell development was assessed. Oct-1 positively regulates the enhancer in pre-B and B cells, while BSAP is a repressor in pre-B cells and an activator at the B cell stage. These studies identify kappa B binding proteins as key modulators of 3'alpha E(hs1,2) and 3'alpha-hs4, and suggest coregulation of the two enhancers by a common set of factors.