bluuebunny/crossref_metadata_2025_split huggingface dataset:
Calcitonin gene-related peptide is necessary for ultraviolet B-impaired induction of contact hypersensitivity.
Authors: Niizeki H , Alard P , Streilein J W 
Published: December 2022

Abstract
Since nerve termini on Langerhans cells (LC) contain calcitonin gene-related peptide (CGRP), and since ultraviolet B radiation (UVR) causes CGRP to be released from cutaneous nerve endings, we examined whether CGRP participates in the immune aberrations caused in skin by UVR. First, intradermally injected CGRP, in a dose-dependent manner, reduced LC density and impaired CH induction when hapten was painted on the injected site. Second, CGRP antagonist restored CH induction after UVR. Third, anti-TNF-alpha Abs injected before CGRP prevented the loss of LC density and restored CH induction. Fourth, CGRP failed to impair CH induction in mast cell-deficient mice. Fifth, CGRP induced mast cells to release TNF-alpha. We conclude that CGRP plays an essential role in the loss of CH induction after UVR. These data indicate that UVR, by causing the release of CGRP from cutaneous nerve endings, triggers mast cell release of TNF-alpha, which impairs CH induction.
Induction of HLA-A2-restricted CTLs to the mucin 1 human breast cancer antigen.
Authors: Apostolopoulos V , Karanikas V , Haurum J S , McKenzie I F 
Published: December 2022

Abstract
HLA-A*0201/Kb transgenic mice were immunized with oxidized mannan-mucin 1 (MUC1) as a fusion protein (containing five repeats of the 20-amino-acid MUC1 VNTR (variable number of tandem repeats) that generated highly active CD8+ CTLs to MUC1 peptides. In a direct CTL assay, the MUC1 peptides could be presented specifically by both the transgenic murine HLA-A*0201/Kb and human HLA-A*0201 molecules. The 9-mer MUC1 peptide sequences (APDTRPA and STAPPAHGV) were presented by HLA-A*0201, although they did not contain L at P2 and L/V at P9, the preferred motifs; as a consequence, the binding was of relatively low affinity when compared with a high affinity-binding HIV peptide (ILKEPVHGV). In addition, when mice were immunized separately with the HLA-A*0201-binding peptides (STAPPAHGV or APDTRPAP-containing peptides-keyhole limpet hemocyanin-mannan), direct lysis of MCF-7 (HLA-A*0201+, MUC1+) also occurred. The findings are of interest for tumor immunotherapy, particularly as the CTLs generated to low affinity-binding peptides were highly active and could specifically lyse an HLA-A*0201+ human breast cancer cell line without further in vitro stimulation. The findings demonstrate that the range of peptides that can generate CTLs is broader than formerly considered.
Apoptotic cell death upon contact of CD4+ T lymphocytes with HIV glycoprotein-expressing cells is mediated by caspases but bypasses CD95 (Fas/Apo-1) and TNF receptor 1.
Authors: Ohnimus H , Heinkelein M , Jassoy C 
Published: December 2022

Abstract
Loss of CD4+ T helper lymphocytes is central to the development of immunodeficiency after infection with HIV. In this study, we demonstrate that contact of primary uninfected CD4+ T lymphocytes with HIV-infected or HIV envelope glycoprotein-expressing cells results in apoptotic cell death of both uninfected and infected cells. Apoptosis was blocked by inhibitors of caspases/IL-1beta-converting enzyme-like proteases. This finding provides conclusive evidence that cytotoxicity upon contact of HIV-infected and uninfected primary cells is an active process and represents another example for the role of caspases in the induction of apoptosis. Prevention of apoptosis by inhibition of caspases did not block the formation of syncytia, indicating that apoptosis occurs either in a subpopulation of cells or in syncytia. Cell death was not mediated by the CD95 (Fas/Apo-1) or TNF receptor 1 molecules, which indicates a different pathway of apoptosis induction. The data indicate that initiation of apoptosis significantly shortens the life span of uninfected CD4+ T cells upon contact with HIV-infected cells and may represent a factor that contributes to the destruction of CD4+ T lymphocytes in vitro. Elucidation of the mechanism that initiates apoptosis in this situation will add to our understanding of both HIV pathogenesis and apoptotic signaling.
Identification of two distinct populations of dendritic cells in afferent lymph that vary in their ability to stimulate T cells.
Authors: Howard C J , Sopp P , Brownlie J , Kwong L S , Parsons K R , Taylor G 
Published: December 2022

Abstract
Immunofluorescent staining and flow cytometric analysis of dendritic cells from cattle afferent lymph has established that within the afferent lymph veiled cells (ALVC) there are two phenotypically distinct, major populations. One is CD11a+, CD5+, CD21- and expresses the bovine WC10 (workshop cluster 10) molecule and the Ag recognized by mAb CC81 but is not recognized by mAbs CC149 and IL-A24. The second ALVC subpopulation is CD11a-, CD5-, CD21+/-, workshop cluster 10- and is not recognized by mAb CC81 but is recognized by mAb CC149. Thus, the two populations, which can be identified by staining for CD11a, are defined by the differential expression of a number of Ag. The ALVC populations had differing capacities to stimulate T cells. CD11a- ALVC were more effective at stimulating proliferative responses in allogeneic CD4+ T cells and CD8+ T cells. This was not related to binding of CTLA4Ig or CD40L fusion proteins, implying similar levels of expression of their ligands, CD80 and CD86 or CD40. Both subsets were able to present OVA to resting memory CD4+ T cells, indicating that both were able to take up and process soluble native protein. In contrast, the CD11a- ALVC were more effective in presenting respiratory syncytial virus Ag to resting CD4+ T cells. Considering the central role of dendritic cells in the initiation of immune responses in naive animals, the two cell types may have different roles in the induction of primary responses induced following infection or immunization.
Evidence for multiple promoters of the human IL-5 receptor alpha subunit gene: a novel 6-base pair element determines cell-specific promoter function.
Authors: Zhang J , Kuvelkar R , Cheewatrakoolpong B , Williams S , Egan R W , Billah M M 
Published: December 2022

Abstract
In addition to a previously characterized promoter (P1), we now show the existence of a second promoter for the human IL-5Ralpha gene. Initially, a genomic region (P2) 5' upstream of human IL-5Ralpha exon 2 was cloned by an inverted PCR. The transcriptional start site was then mapped to a deoxycytidine (C) residue within P2 by analyzing cellular mRNA with both the 5' rapid amplification of cDNA end-PCR and S1 nuclease protection assays. Transfection of eosinophilic HL-60 cells with reporter gene constructs in which either P1 or P2 was linked to the bacterial chloramphenicol acetyltransferase (CAT) gene resulted in CAT expression; little or no CAT expression occurred in other myeloid and nonmyeloid cell lines. Deletion studies showed that a 66-bp region, ranging from -31 to +35, was sufficient to promote CAT expression in eosinophilic HL-60 cells. Analysis of linker-scanning mutants identified a novel 6-bp element (5' CTAATT 3') spanning -19 to -14 that was essential for P2 promoter activity. In electrophoretic mobility shift assays, a P2 region from -31 to +1 containing the unique 6-bp element, when used as a probe, formed a complex with a protein(s) that was found only in the eosinophilic cell line. This binding activity was lost upon replacement of the 6-bp element with a 6-bp linker, suggesting that this element likely serves as the binding site for an eosinophilic HL-60 cell-specific transcription factor(s). Together, these data suggest an important role for P2 promoter in the regulation of eosinophil-specific expression of the human IL-5 receptor alpha gene.
IL-4-induced STAT6 suppresses IFN-gamma-stimulated STAT1-dependent transcription in mouse macrophages.
Authors: Ohmori Y , Hamilton T A 
Published: December 2022

Abstract
IL-4 suppresses the IFN-gamma-induced expression of the IFN regulatory factor-1 (IRF-1) gene, and this suppression is attenuated by increasing the amount of IFN-gamma. The effects of IFN-gamma and IL-4 on transcription of a reporter gene under control of a 1.3-kb fragment from the IRF-1 gene promoter or the STAT binding element (SBE) from this gene in the context of a heterologous promoter are similar to their effects on the endogenous IRF-1 gene. IFN-gamma-dependent transcription of reporter gene is suppressed by IL-4, but IL-4 alone has no trans-activating function. IL-4 treatment does not inhibit the tyrosine phosphorylation or nuclear translocation of IFN-gamma-activated STAT1. Rather, IFN-gamma and IL-4 independently activate STAT1 and STAT6, respectively, and both proteins bind to the IRF-1 SBE in homodimeric form. The affinity of STAT1 for the IRF-1 SBE is higher than the affinity of STAT6, as measured by competition with unlabeled oligonucleotide. These observations suggest that IL-4 may suppress IFN-gamma-stimulated transcription of the IRF-1 gene by activation of STAT6, which can compete with STAT1 for occupancy of the IRF-1 SBE when STAT1 levels are low. Suppression may be attenuated as the quantity of STAT1 relative to that of STAT6 increases in cells treated with increasing amounts of IFN-gamma and displaces STAT6.
IL-18 protects mice against pulmonary and disseminated infection with Cryptococcus neoformans by inducing IFN-gamma production.
Authors: Kawakami K , Qureshi M H , Zhang T , Okamura H , Kurimoto M , Saito A 
Published: December 2022

Abstract
We examined the effects of a newly identified cytokine, IL-18, originally designated as IFN-gamma-inducing factor, in a mouse model of pulmonary and disseminated infection with a highly virulent strain of Cryptococcus neoformans. Administration of murine rIL-18 enhanced elimination of live micro-organisms from the lungs, prevented fungal dissemination to the brain, reduced the level of serum cryptococcal capsular polysaccharide Ags, and increased the survival rate of infected mice. Histologic examination of lung sections of infected and PBS-treated mice showed a poor cellular inflammatory reaction and a large number of multiplying C. neoformans yeast cells in alveolar spaces. In contrast, massive infiltration of inflammatory cells, consisting mainly of mononuclear cells, characterized sections of lungs of infected animals treated with IL-18. Treatment with IL-18 also increased the level of serum IFN-gamma. In addition, the protective effect of IL-18 on cryptococcal infection was abrogated by administration of neutralizing anti-IFN-gamma mAb. Finally, we examined the effect of neutralizing anti-IL-18 Ab on cryptococcal infection to define the physiologic role of this cytokine in host defense using another weakly virulent strain of C. neoformans, which induced the expression of IL-18 mRNA in the infected lungs. Administration of this Ab exacerbated the infection, as shown by the increased lung burden. Our results indicate that IL-18 plays an important role in host defense against infection with C. neoformans.
Interchangeable endotoxin-binding domains in proteins with opposite lipopolysaccharide-dependent activities.
Authors: Schumann R R , Lamping N , Hoess A 
Published: December 2022

Abstract
Host defense against microorganisms involves proteins that bind specifically to bacterial endotoxins (LPS), causing different cellular effects. Although LPS-binding protein (LBP) can enhance LPS activities, while bactericidal/permeability-increasing protein (BPI) and Limulus anti-LPS factor (LALF) neutralize LPS, it has been proposed that their LPS-binding domains possess a similar structure. Here, we provide evidence that the LBP/LPS-binding domain is, as in the LALF structure, solvent exposed and therefore available for LPS binding. Our investigations into the activity of LPS-binding domains of different LPS-binding proteins, in the context of LBP, provide the first functional analysis of these domains in a whole protein. We constructed domain exchange hybrid proteins by substituting 12 amino acids of the LBP/LPS-binding domain with those of BPI and LALF and expressed them in Chinese hamster ovary cells. Although discrete point mutations within the LPS-binding domain of LBP disrupted its specific functions, the hybrid proteins were still able to bind LPS and, in addition, retained the wild-type LBP activity of enhancing LPS priming for FMLP-induced oxygen radical production by neutrophils and transferring LPS aggregates to CD14. Although BPI and LALF display opposite activities to LBP, and LALF does not share any sequence homology with LBP, our data provide strong evidence that LBP, BPI, and LALF possess a solvent-exposed, interchangeable LPS binding motif that is functionally independent of LPS transport or neutralization.
Human alternative complement pathway-mediated lysis of rabbit erythrocytes is enhanced by natural anti-Galalpha1-3Gal antibodies.
Authors: Tomlinson S , Nussenzweig V 
Published: December 2022

Abstract
Human serum is effective at lysing unsensitized rabbit erythrocytes due to activation of the alternative complement pathway. Hemolysis is known to be enhanced by the addition of human IgG. We demonstrate that the enhancement of alternative pathway-mediated rabbit E lysis by human Ig is due to natural Abs specific for galactosyl (Gal)alpha1-3Gal. Depletion of normal human serum (NHS) of anti-Galalpha1-3Gal Abs removes almost all hemolytic activity from NHS, and activity can be restored by repletion with anti-Galalpha1-3Gal affinity-purified Abs. Factor B-depleted serum (inactive alternative pathway) did not lyse rabbit erythrocytes. Although C2-depleted serum was fully hemolytic, activity was removed by depletion of anti-Galalpha1-3Gal Abs. Of the total anti-Galalpha1-3Gal Abs affinity isolated from NHS, about one-third were IgM and two-thirds were IgG. Both anti-Galalpha1-3Gal IgG and IgM enhanced alternative pathway-mediated erythrocyte lysis.
Do effector and memory T helper cells also need B7 ligand costimulatory signals?
Authors: Gause W C , Mitro V , Via C , Linsley P , Urban J F , Greenwald R J 
Published: December 2022

Abstract
Blocking B7 ligand-costimulatory molecules can inhibit a primary T-dependent immune response, but whether these interactions also mediate ongoing or memory immune responses is less clear. Development of immunotherapies based on blocking B7 ligand interactions would be limited if they were effective only at the initiation of an immune response. We discuss the conditions under which T helper effector and memory cells may or may not require B7 ligand interactions for their function.
Inhibition of acute peritoneal inflammation in rats by a cytokine-induced neutrophil chemoattractant receptor antagonist.
Authors: Zagorski J , Wahl S M 
Published: December 2022

Abstract
Cytokine-induced neutrophil chemoattractant (CINC), a member of the IL-8 superfamily of chemokines, is one rat homologue of the three human GRO proteins. Neutralizing Abs against CINC have been shown previously to be efficacious in several models of inflammation, indicating that CINC is an important proinflammatory mediator in vivo. By introducing the N-terminal mutation delta1-5,ELR&gt;AAR into CINC, we have developed a rat alpha-chemokine receptor antagonist (ra) analogous to a previously described mutant of human IL-8. Bacterially expressed CINCra had no chemotactic activity itself, but completely blocked the activity of physiologic concentrations of CINC when used as an antagonist in vitro. Inhibition by CINCra was specific, since it had approximately 10-fold less antagonist activity on the related, but distinct rat alpha-chemokine macrophage-inflammatory protein 2. When coinjected with zymosan into the peritoneal cavities of Lewis rats, 100 microg of CINCra inhibited neutrophil influx by approximately 40%, which was comparable with inhibition caused by polyclonal anti-CINC Abs.
B cell responses to a peptide epitope: III. Differential T helper cell thresholds in recruitment of B cell fine specificities.
Authors: Agarwal A , Rao K V 
Published: December 2022

Abstract
Th cell requirements in the individual stages comprising a murine humoral response to a synthetic peptide were examined. Induction of a T-dependent IgM response was readily achieved in the presence of unprimed or low numbers of Ag-primed T cells. In contrast, class switch to the IgG isotype of Abs demanded a markedly elevated frequency of primed T cells and occurred concomitantly with B cell differentiation into an membrane-bound IgG+ memory population. These results indicated that induction and progression of a T-dependent humoral IgG response were comprised of a single rate-limiting step represented by that involving Ab isotype switch. Subsequent studies established that this also represented the principal step where antibody-purifying mechanisms operate. This was enforced by imposing a threshold barrier for Th cell recruitment by early Ag-activated B cells to enable class switch and consequent retention as the response progresses. The quantum of this threshold, however, was not invariant, but, rather, was described as a balance between the affinity of B cell receptor for Ag and the frequency of Ag-specific Th cells.
ZAP-70 tyrosine kinase is required for the up-regulation of Fas ligand in activation-induced T cell apoptosis.
Authors: Eischen C M , Williams B L , Zhang W , Samelson L E , Lynch D H , Abraham R T , Leibson P J 
Published: December 2022

Abstract
Activation-induced cell death (AICD) is initiated by the TCR-dependent up-regulation of Fas ligand (FasL) mRNA. The subsequently generated soluble or cell-associated FasL gene products bind Fas, leading to apoptosis of the T cells. Although TCR stimulation is essential to initiate AICD, little is known about which TCR-initiated second messengers are required for FasL expression. We provide evidence in this work that T cells lacking the tyrosine kinase ZAP-70 are unable to up-regulate FasL and undergo AICD. Transfection of wild-type ZAP-70 into the ZAP-70-deficient T cells restores their sensitivity to TCR-induced apoptosis, whereas transfection of catalytically inactive ZAP-70 does not. These results provide clear evidence that ZAP-70 tyrosine kinase is essential in up-regulating FasL for TCR-induced apoptosis.
RP1, a new member of the adenomatous polyposis coli-binding EB1-like gene family, is differentially expressed in activated T cells.
Authors: Renner C , Pfitzenmeier J P , Gerlach K , Held G , Ohnesorge S , Sahin U , Bauer S , Pfreundschuh M 
Published: December 2022

Abstract
Cross-linking of the CD3 and CD28 molecules on T lymphocytes represents one of the most effective signals for T lymphocyte activation and triggering of their cytotoxic effector function. To identify genes that are expressed in T cells after stimulation, mRNA from T lymphocytes that had been activated by the simultaneous stimulation of the CD3 and CD28 trigger molecules was transcribed for a differential mRNA display analysis into cDNA and was compared with cDNA from CD28- or CD3-activated or resting lymphocytes. Differential expression was confirmed subsequently by Northern blot analysis. One of the cDNA fragments expressed specifically in CD3- and CD28-activated T cells was designated RP1. The predictive protein-coding region of RP1 had a significant homology to members of the recently found adenomatous polyposis coli (APC) protein-binding EB1 gene family, which codes for yet unknown protein(s). Bacterially expressed RP1 protein revealed specific binding to wild-type but not to mutated APC protein. The rapid up-regulation of RP1 mRNA in properly activated T cells suggests that this gene might belong to the immediate/early gene family, which controls the signal transduction cascade downstream of the TCR. As the expression level of the RP1 gene in activated T cells and a spectrum of tumor-derived cell lines correlates with the proliferative status of the cells, members of the EB1-like gene family may not only be involved in the tumorigenesis of colorectal cancers but may also play a role in the proliferative control of normal cells.
Peptides derived from a wild-type murine proto-oncogene c-erbB-2/HER2/neu can induce CTL and tumor suppression in syngeneic hosts.
Authors: Nagata Y , Furugen R , Hiasa A , Ikeda H , Ohta N , Furukawa K , Nakamura H , Furukawa K , Kanematsu T , Shiku H 
Published: December 2022

Abstract
In this analysis, we examined whether peptides derived from a wild-type murine proto-oncogene, c-erbB-2, function as tumor rejection Ags. Expression of murine c-erbB-2 examined by means of reverse transcription-PCR was observed in several normal adult tissues, such as intestine, kidney, and testis. We then transduced human and murine c-erbB-2 cDNA into two mutually noncross-reactive fibrosarcoma lines of BALB/c origin, CMS7 and CMS17. In BALB/c mice immunized with CMS17HE (CMS17 transduced with human c-erbB-2 cDNA), the growth of subsequently challenged CMS7HE (CMS7 transduced with human c-erbB-2 cDNA) was significantly suppressed. CTL against human c-erbB-2-expressing cells were generated from BALB/c spleen cells in vivo and in vitro sensitized by CMS17HE. The CTL activity was also directed against murine c-erbB-2-expressing cells, CMS7ME and CMS17ME, and was blocked by anti-CD8 or anti-Kd mAbs. A series of peptides of human or murine c-erbB-2 compatible with the Kd binding motif was synthesized. The CTL were reactive with P1.HTR (H-2d) pulsed with three of these peptides, p63-71 (human c-erbB-2 derived), p63-71(A) (murine c-erbB-2 derived), and p780-788 (common for human and murine c-erbB-2). Spleen cells immunized in vivo and in vitro with syngeneic spleen cells pulsed with these peptides became cytotoxic for CMS17HE and/or CMS17ME, but not CMS17neo (CMS17 transduced with control vector). The growth of CMS7ME was suppressed in mice immunized with the murine c-erbB-2-derived peptide, p63-71(A) or p780-788. There was no apparent pathologic change in mice that rejected CMS7ME after vaccination with these peptides.
Binding of malaria T cell epitopes to DR and DQ molecules in vitro correlates with immunogenicity in vivo: identification of a universal T cell epitope in the Plasmodium falciparum circumsporozoite protein.
Authors: Calvo-Calle J M , Hammer J , Sinigaglia F , Clavijo P , Moya-Castro Z R , Nardin E H 
Published: December 2022

Abstract
The efficacy of a malaria peptide vaccine would be enhanced by the inclusion of a parasite-derived universal T cell epitope to ensure that all vaccinees develop parasite-specific cellular and humoral immunity. Two circumsporozoite (CS) protein T cell epitopes, previously identified by CD4+ T cell clones derived from Plasmodium falciparum sporozoite-immunized volunteers, were studied to determine their HLA class II binding potential. One epitope, located in amino acid (aa) 326-345 of the P. falciparum (NF54 strain) CS protein, was "universal" in that it could bind to multiple DR and DQ molecules in vitro. In contrast, the second epitope, T1, which is located in the CS repeat region, was recognized by T cells in the context of DQ6 (DQB1*0603) and did not bind with high affinity to any of the class II molecules tested in the peptide binding assays. The in vitro patterns of peptide/HLA interactions correlated with immunogenicity in vivo. A multiple antigen peptide (MAP) containing the aa 326-345 epitope elicited responses in eight inbred strains (H-2(a,b,d,k,p,q,r,s)), while the T1 MAP was recognized by only a single haplotype, H-2b. The combination of the universal aa 326-345 T cell epitope and the T1 repeat in a di-epitope MAP overcame the genetic restriction to the P. falciparum CS repeat region and elicited antisporozoite Ab responses in all of the MAP-immunized mice. Synthetic peptide malaria vaccines containing the aa 326-345 universal T cell epitope would be expected to elicit parasite-specific immune responses in both sporozoite-primed and naive individuals of diverse genetic backgrounds.