bluuebunny/crossref_metadata_2025_split huggingface dataset:
Innate Immunity in Insects: The Role of Multiple, Endogenous Serum Lectins in the Recognition of Foreign Invaders in the Cockroach, Blaberus discoidalis
Authors: Wilson Raymond , Chen Changwei , Ratcliffe Norman A. 
Published: December 2022

Abstract
Unlike vertebrates, insects do not have an Ab-based nonself recognition system, and must rely totally on innate immunity to defend themselves from microbial invaders. The most likely candidates for recognizing foreign material in insects are the lectins, which have already been shown to be important in mammalian innate immunity. The hemolymph of the cockroach, Blaberus discoidalis, contains multiple lectins, designated BDL1, BDL2, BDL3, and GSL (β-1,3-glucan-specific lectin), two of which, namely BDL1 and GSL, have close similarities to acute phase reactants. These endogenous molecules, as well as Con A, wheat germ agglutinin, and Helix pomatia agglutinin, have been shown to induce an enhanced phagocytic response by B. discoidalis plasmatocytes. This effect is related to the carbohydrates presented on the surface of the microorganism and to the sugar specificities of the lectins. Thus, the mannose-specific lectins, BDL1 and Con A, both increase the phagocytosis of baker’s yeast and Escherichia coli, whereas the N-acetyl-d-glucosamine/N-acetyl-d-galactosamine-specific lectins, BDL2, wheat germ agglutinin, and H. pomatia agglutinin, induce the phagocytosis of Bacillus cereus and E. coli. GSL, specific for β-1,3-glucan, and the N-acetyl-d-galactosamine-specific BDL3, only enhance the phagocytosis of yeast and B. cereus, respectively. Phenylthiourea, an inhibitor of the prophenoloxidase system, caused either total, partial, or no inhibition of the lectin-induced increase in phagocytosis, indicating that this immune enhancement results, in some cases, from at least two closely linked mechanisms. These results show that the endogenous lectins in the cockroach hemolymph are capable of acting as nonself recognition molecules for a wide range of microorganisms, and thus obviate the necessity of Abs in these animals.
Mucosal DNA Vaccine Immunization Against Measles with a Highly AttenuatedShigella flexneriVector
Authors: Fennelly Glenn J. , Khan Shibber A. , Abadi Maria A. , Wild T. Fabian , Bloom Barry R. 
Published: December 2022

AbstractAn intranasal vaccine vector would elicit protective immunity at the respiratory mucosa, the portal of entry and the primary site for replication for measles virus (MV) and other respiratory viruses. In a murine model of pulmonary Shigella, we demonstrate here that a candidate-attenuated Shigella vaccine vector is safely tolerated in IFN-γ deficient mice at an inoculum that is 1 million-fold higher than the inoculum of the wild-type parent strain that would be lethal for greater than 90% of these mice. Also, following intranasal inoculation, the Δasd Shigella harboring a DNA MV vaccine plasmid induces a vigorous MV-specific Th1-type (both CD8+ CTL and IFN-γ) and, to a lesser degree, Th2-type responses among splenocytes in addition to low levels of IgG and IgA in the serum. Priming for MV-specific CTL responses was possible in mice that had prior infection with a wild-type Shigella of the same serotype. Remarkably, mice immunized by the intranasal route with attenuated Shigella harboring the DNA MV vaccine plasmid had a level of MV-specific CTL activity among splenocytes that was comparable with levels observed in mice immunized by the i.p. route with attenuated Salmonella typhi harboring the same DNA vaccine plasmid, despite the fact that Shigella remained localized to the lungs, yet Salmonella disseminated to the spleen following inoculation. Thus, Δasd Shigella represents a very useful vector for delivery of DNA vaccines to mucosal lymphoid tissues.
Role of Resident Peritoneal Macrophages and Mast Cells in Chemokine Production and Neutrophil Migration in Acute Inflammation: Evidence for an Inhibitory Loop Involving Endogenous IL-10
Authors: Ajuebor Maureen N. , Das Anuk M. , Virág László , Flower Roderick J. , Szabó Csaba , Perretti Mauro 
Published: December 2022

AbstractThe roles played by resident macrophages (Mφ) and mast cells (MCs) in polymorphonuclear leukocyte (PMN) accumulation and chemokine production within the mouse peritoneal cavity in response to administration of zymosan (0.2 and 1 mg), LPS (1 mg/kg), and thioglycolate (0.5 ml of a 3% suspension) were investigated. A marked reduction (&gt;95%) in intact MC numbers was obtained by pretreatment with the MC activator compound 48/80, whereas resident Mφ were greatly diminished (&gt;85%) by a 3-day treatment with liposomes encapsulating the cytotoxic drug dichloromethylene-bisphosphonate. No modulation of thioglycolate-induced inflammation was seen with either pretreatment. Removal of either MCs or Mφ attenuated LPS-induced PMN extravasation without affecting the levels of the chemokines murine monocyte chemoattractant protein-1 and KC measured in the lavage fluids. In contrast, MC depletion inhibited PMN accumulation and murine monocyte chemoattractant protein-1 and KC production in the zymosan peritonitis model. Removal of Mφ augmented the accumulation of PMN elicited by the latter stimulus. This was due to an inhibitory action of Mφ-derived IL-10 because there was 1) a time-dependent release of IL-10 in the zymosan exudates; 2) a reduction in IL-10 levels following Mφ, but not MC, depletion; and 3) an increased PMN influx and chemokine production in IL-10 knockout mice. In conclusion, we propose a stimulus-dependent role of resident MCs in chemokine production and the existence of a regulatory loop between endogenous IL-10 and the chemokine-mediated cellular component of acute inflammation.
Novel HLA-Cw8-Restricted T Cell Epitopes Derived from Tyrosinase-Related Protein-2 and gp100 Melanoma Antigens
Authors: Castelli Chiara , Tarsini Paolo , Mazzocchi Arabella , Rini Francesca , Rivoltini Licia , Ravagnani Fernando , Gallino Francesco , Belli Filiberto , Parmiani Giorgio 
Published: December 2022

AbstractThe identification of T cell epitopes presented by alternative HLA-B and -C alleles may provide a means to counteract the tumor escape mechanism based on the selection of tumor cells no longer susceptible to HLA-A-restricted T cell recognition. Several T cell clones and lines were obtained from T lymphocytes purified from melanoma-infiltrated or noninfiltrated lymph nodes of a patient who remained disease free 8 yr after surgery. Selected T cells recognized the autologous melanoma as evaluated by direct cytolysis and production of cytokines. These effectors were directed against the tyrosinase-related protein-2 (TRP-2) and gp100 melanoma epitopes restricted by HLA-Cw8. The nonamer and decamer peptides containing the sequence ANDPIFVVL (residues 387–395) of TRP-2 and the octamer, nonamer, and decamer peptides containing the sequence SNDGPTLI (residues 71–78) of gp100 reconstituted the epitope for TRP-2- and gp100-specific T cell lines and clones, respectively. However, only the nonameric form of TRP-2 and the nonameric and octameric forms of gp100 were able to induce peptide-specific T cells recognizing the autologous tumor in an HLA-class I-restricted fashion from PBMC of the melanoma patient studied. Together these data indicate that HLA-Cw8 can restrict the recognition of gp100 and TRP-2 epitopes by CTL, and that such peptides could stimulate a patient’s PBL, suggesting that these Ags could have contributed to a systemic immunity against melanoma.
Changes in the Fine Specificity of gp100(209–217)-Reactive T Cells in Patients Following Vaccination with a Peptide Modified at an HLA-A2.1 Anchor Residue
Authors: Clay Timothy M. , Custer Mary C. , McKee Mark D. , Parkhurst Maria , Robbins Paul F. , Kerstann Keith , Wunderlich John , Rosenberg Steven A. , Nishimura Michael I. 
Published: December 2022

AbstractIn a recent clinical trial, HLA-A2+ melanoma patients were vaccinated with a peptide derived from the melanoma Ag gp100, which had been modified at the second position (g9-209 2M) to enhance MHC binding affinity. Vaccination led to a significant increase in lymphocyte precursors in 10 of 11 patients but did not result in objective cancer responses. We observed that some postvaccination PBMC cultures were less reactive with tumor cells than they were with g9-209 peptide-pulsed T2 cells. In contrast, g9-209-reactive tumor-infiltrating lymphocyte cultures generally reacted equally with tumor cells and g9-209 peptide-pulsed T2 cells. To investigate this difference in T cell reactivity, T cell cloids derived from the PBMC of three patients vaccinated with g9-209 2M were compared with T cell cloids isolated from g9-209-reactive TIL cultures. All of the T cell cloids obtained from TIL reacted with HLA-A2+, gp100+ melanoma cell lines as well as with g9-209 and g9-209 2M peptide-pulsed targets. In contrast, only 3 of 20 PBMC-derived T cell cloids reacted with melanoma cell lines in addition to g9-209 and to g9-209 2M peptide-pulsed targets. Twelve of twenty PBMC-derived cloids reacted with g9-209 and g9-209 2M peptide-pulsed targets but not with melanoma cell lines. And 5 of 20 PBMC-derived cloids recognized only the g9-209 2M-modified peptide-pulsed targets. These results suggest that immunizing patients with the modified peptide affected the T cell repertoire by expanding an array of T cells with different fine specificities, only some of which recognized melanoma cells.
Direct Analysis of Viral-Specific CD8+ T Cells with Soluble HLA-A2/Tax11-19 Tetramer Complexes in Patients with Human T Cell Lymphotropic Virus-Associated Myelopathy
Authors: Bieganowska Katarzyna , Höllsberg Per , Buckle Guy J. , Lim Dong-Gyun , Greten Tim F. , Schneck Jonathan , Altman John D. , Jacobson Steven , Ledis Stephen L. , Hanchard Barrie , Chin Jonathan , Morgan Owen , Roth Patricia A. , Hafler David A. 
Published: December 2022

AbstractHuman T cell lymphotropic virus-I (HTLV-I)-associated myelopathy is a slowly progressive neurologic disease characterized by inflammatory infiltrates in the central nervous system accompanied by clonal expansion of HTLV-I-reactive CD8+ T-cells. In patients carrying the HLA-A2 allele, the immune response is primarily directed to the Tax11-19 peptide. The frequency, activation state, and TCR usage of HLA-A2/Tax11-19 binding T cells in patients with HTLV-I-associated myelopathy was determined using MHC class I tetramers loaded with the Tax11-19 peptide. Circulating Tax11-19-reactive T cells were found at very high frequencies, approaching 1:10 circulating CD8+ T cells. T cells binding HLA-A2/Tax11-19 consisted of heterogeneous populations expressing different chemokine receptors and the IL-2R β-chain but not the IL-2R α-chain. Additionally, Tax11-19-reactive CD8+ T cells used one predominant TCR Vβ-chain for the recognition of the HLA-A2/Tax11-19 complex. These data provide direct evidence for high frequencies of circulating Tax11-19-reactive CD8+ T cells in patients with HTLV-I-associated myelopathy.
Immune-Mediated Destruction of Melanocytes in Halo Nevi Is Associated with the Local Expansion of a Limited Number of T Cell Clones
Authors: Musette Philippe , Bachelez Hervé , Flageul Béatrice , Delarbre Christiane , Kourilsky Philippe , Dubertret Louis , Gachelin Gabriel 
Published: December 2022

Abstract
The β-chain repertoire of the T cells that infiltrate spontaneously regressing nevi (the halo nevus phenomenon) was studied. In addition to the infiltration of the halo nevi by cutaneous lymphocyte-associated Ag-positive lymphocytes, oligoclonal expansion of T cells was observed in all halo nevi of all patients. T cells using the same TCR β-chain were observed in distinct halo nevi of the same patient but not in his peripheral blood, demonstrating a local expansion of common clones that are most likely activated by the Ag(s) shared by independent halo nevi of the same patient.
Signs of Immaturity of Splenic Dendritic Cells from the Autoimmune Prone Biobreeding Rat: Consequences for the In Vitro Expansion of Regulator and Effector T Cells
Authors: Delemarre Frans G. A. , Simons Peter J. , de Heer Hendrik Jan , Drexhage Hemmo A. 
Published: December 2022

AbstractFrom the biobreeding-diabetic prone (BB-DP) rat, an animal model for endocrine autoimmunity, phenotype and function of splenic dendritic cells (DC) were studied. Furthermore, the suppressive effect of peritoneal macrophages (pMφ) from the BB-DP rat in the MLR was investigated. Lower numbers of splenic DC were isolated from BB-DP rats than from control Wistar rats. In the preautoimmune phase, DC of the BB-DP rat had a lower surface MHC class II expression (and in preliminary data, a lower CD80 expression), ingested more bacteria, and had a lower stimulatory potency in the syngeneic (syn)MLR as compared with control DC. During disease development, the MHC class II expression further decreased, and a low stimulatory activity became evident in the allogeneic (allo)MLR. With regard to the expansion of suppressor/regulatory T cells, a lower percentage of RT6+ T cells but higher percentages of CD45RClow T cells were induced by BB-DP DC in synMLR, but not in alloMLR. An increase in the CD4/CD8 T cell ratio was observed in both the syn- and alloMLR due to a relative weak expansion of CD8+ T cells with DC of the BB-DP rat. Resident pMφ isolated from BB-DP or Wistar rats were equally effective in suppressing the DC-driven synMLR. In conclusion, splenic DC from the BB-DP rat have a lower accessory cell function already at young age, before the development of disease, and expanded different subsets of effector/suppressor T cells in vitro as compared with those from Wistar rats. The dysfunction of DC from BB-DP rats is likely to be caused by their relative immaturity as indicated by their low class II and costimulatory molecule expression and relatively high phagocytic activity.
Blocking OX-40/OX-40 Ligand Interaction In Vitro and In Vivo Leads to Decreased T Cell Function and Amelioration of Experimental Allergic Encephalomyelitis
Authors: Weinberg Andrew D. , Wegmann3 Keith W. , Funatake Castle , Whitham Ruth H. 
Published: December 2022

AbstractThe OX-40R is a member of the TNF receptor family and is expressed primarily on activated CD4+ T cells. When the OX-40R is engaged by the OX-40 ligand (OX-40L), a potent costimulatory signal occurs. We have identified a population of CD11b+ cells, isolated from the central nervous system (CNS) of mice with actively induced experimental allergic encephalomyelitis (EAE), that expresses OX-40L. Moreover, the expression of OX-40L was found to be associated with paralytic episodes of EAE and was reduced or absent at disease recovery. These CD11b+ cells also coexpressed B7 and MHC class II. Therefore, to address the relative contributions of OX-40R/OX-40L and CD28/B7 to the costimulation of myelin-specific T cells, blocking studies were performed using soluble OX-40R and/or soluble CTLA-4. CD11b+ cells isolated from the CNS of mice with actively induced EAE were able to present Ag to proteolipid protein 139–151-specific T cell lines in vitro. The addition of soluble OX-40R:Ig to CD11b+ brain microglia/macrophages inhibited T cell proliferation by 50–70%. The addition of CTLA-4:Ig inhibited T cell proliferation by 20–30%, and the combination inhibited T cell proliferation by 95%. In vivo administration of soluble OX-40R at the onset of actively induced or adoptively transferred EAE reduced ongoing signs of disease, and the mice recovered more quickly from acute disease. The data imply that OX-40L, expressed by CNS-derived APC, acts to provide an important costimulatory signal to EAE effector T cells found within the inflammatory lesions. Furthermore, the data suggest that agents designed to inhibit the OX-40L/OX-40R complex may be useful for treating autoimmune disease.
Cutting Edge: A Role for the Adaptor Protein LAT in Human NK Cell-Mediated Cytotoxicity
Authors: Jevremovic Dragan , Billadeau Daniel D. , Schoon Renee A. , Dick Christopher J. , Irvin Brenda J. , Zhang Weiguo , Samelson Lawrence E. , Abraham Robert T. , Leibson Paul J. 
Published: December 2022

AbstractStimulation of NK cell-mediated cytotoxicity involves the coupling of proximal Src and Syk family protein tyrosine kinases to downstream effectors. However, the mechanisms linking these second messenger pathways are incompletely understood. Here, we describe a key role for the LAT (p36) adaptor protein in human NK cell activation. LAT is tyrosine phosphorylated upon stimulation of NK cells through FcγRIII receptors and following direct contact with NK-sensitive target cells. This NK stimulation induces the association of LAT with several phosphotyrosine-containing proteins. In addition to the biochemical evidence showing LAT involvement in NK cell activation, a genetic model shows that LAT is required for FcR-dependent phosphorylation of phospholipase C-γ. Furthermore, overexpression of LAT in NK cells leads to increased Ab-dependent cell-mediated cytotoxicity and “natural cytotoxicity,” thus demonstrating a functional role for LAT in NK cells. These data suggest that LAT is an important adaptor protein for the regulation of human NK cell-mediated cytotoxicity.
Islet-Specific Th1, But Not Th2, Cells Secrete Multiple Chemokines and Promote Rapid Induction of Autoimmune Diabetes
Authors: Bradley Linda M. , Asensio Valérie C. , Schioetz Li-Karine , Harbertson Judith , Krahl Troy , Patstone Gail , Woolf Nigel , Campbell Iain L. , Sarvetnick Nora 
Published: December 2022

AbstractMigration of CD4 cells into the pancreas represents a hallmark event in the development of insulin-dependent diabetes mellitus. Th1, but not Th2, cells are associated with pathogenesis leading to destruction of islet β-cells and disease onset. Lymphocyte extravasation from blood into tissue is regulated by multiple adhesion receptor/counter-receptor pairs and chemokines. To identify events that regulate entry of CD4 cells into the pancreas, we transferred Th1 or Th2 cells induced in vitro from islet-specific TCR transgenic CD4 cells into immunodeficient (NOD.scid) recipients. Although both subsets infiltrated the pancreas and elicited multiple adhesion receptors (peripheral lymph node addressin, mucosal addressin cell adhesion molecule-1, LFA-1, ICAM-1, and VCAM-1) on vascular endothelium, entry/accumulation of Th1 cells was more rapid than that of Th2 cells, and only Th1 cells induced diabetes. In vitro, Th1 cells were also distinguished from Th2 cells by the capacity to synthesize several chemokines that included lymphotactin, monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-1α, whereas both subsets produced macrophage inflammatory protein-1β. Some of these chemokines as well as RANTES, MCP-3, MCP-5, and cytokine-response gene-2 (CRG-2)/IFN-inducible protein-10 (IP-10) were associated with Th1, but not Th2, pancreatic infiltrates. The data demonstrate polarization of chemokine expression by Th1 vs Th2 cells, which, within the microenvironment of the pancreas, accounts for distinctive inflammatory infiltrates that determine whether insulin-producing β-cells are protected or destroyed.
Characterization of TCR Gene Rearrangements During Adult Murine T Cell Development
Authors: Livák Ferenc , Tourigny Michelle , Schatz David G. , Petrie Howard T. 
Published: December 2022

AbstractDevelopment of the αβ and γδ T cell lineages is dependent upon the rearrangement and expression of the TCRα and β or γ and δ genes, respectively. Although the timing and sequence of rearrangements of the TCRα and TCRβ loci in adult murine thymic precursors has been characterized, no similar information is available for the TCRγ and TCRδ loci. In this report, we show that approximately half of the total TCRδ alleles initiate rearrangements at the CD44highCD25+ stage, whereas the TCRβ locus is mainly in germline configuration. In the subsequent CD44lowCD25+ stage, most TCRδ alleles are fully recombined, whereas TCRβ rearrangements are only complete on 10–30% of alleles. These results indicate that rearrangement at the TCRδ locus can precede that of TCRβ locus recombination by one developmental stage. In addition, we find a bias toward productive rearrangements of both TCRδ and TCRγ genes among CD44highCD25+ thymocytes, suggesting that functional γδ TCR complexes can be formed before the rearrangement of TCRβ. These data support a model of lineage commitment in which sequential TCR gene rearrangements may influence αβ/γδ lineage decisions. Further, because TCR gene rearrangements are generally limited to T lineage cells, these analyses provide molecular evidence that irreversible commitment to the T lineage can occur as early as the CD44highCD25+ stage of development.
IL-15 Induces the Expression of Chemokines and Their Receptors in T Lymphocytes
Authors: Perera Liyanage P. , K. Goldman Carolyn , Waldmann Thomas A. 
Published: December 2022

AbstractIL-15 is a T cell growth factor that shares many biological activities with IL-2 and uses the same β/γ polypeptides of the IL-2R complex for signal transduction. Accumulating evidence implicates an important role for this cytokine in the inflammatory response of the host. Consistent with such a role, IL-15 has been shown to be a chemoattractant for T lymphocytes, NK cells, and neutrophils. Extending these observations, we now show that IL-15 is a potent inducer of CC-, CXC-, and C-type chemokines in T lymphocytes. In addition, we demonstrate that IL-15 induces CC chemokine receptors, but not CXC chemokine receptors, in a dose-dependent manner. Thus, our findings suggest that the proinflammatory effects of IL-15 at least in part may be due to the induction of chemokines and their receptors in T cells. Furthermore, we demonstrate that IL-15 promotes entry and replication of macrophage-tropic HIV in T lymphocytes and suggest a plausible mechanism by which IL-15, a cytokine that is elevated in HIV-infected individuals, may promote the transition of HIV displaying the M-tropic phenotype primarily associated with the initial transmission into the T cell-tropic phenotype that predominates as the disease progresses.
Regulation of B Cell Receptor-Mediated MHC Class II Antigen Processing by FcγRIIB1
Authors: Wagle Neelam M. , Faassen Anne E. , Kim Julie H. , Pierce Susan K. 
Published: December 2022

AbstractThe processing and presentation of Ag by Ag-specific B cells is highly efficient due to the dual function of the B cell Ag receptor (BCR) in both signaling for enhanced processing and endocytosing bound Ag. The BCR for IgG (FcγRIIB1) is a potent negative coreceptor of the BCR that blocks Ag-induced B cell proliferation. Here we investigate the influence of the FcγRIIB1 on BCR-mediated Ag processing and show that coligating the FcγRIIB1 and the BCR negatively regulates both BCR signaling for enhanced Ag processing and BCR-mediated Ag internalization. Treatment of splenic B cells with F(ab′)2 anti-Ig significantly enhances APC function compared with the effect of whole anti-Ig; however, whole anti-Ig treatment is effective when binding to the FcγRIIB1 was blocked by a FcγRII-specific mAb. Processing and presentation of Ag covalently coupled to anti-Ig were significantly decreased compared with Ag coupled to F(ab′)2anti-Ig; however, the processing of the two Ag-Ab conjugates was similar in cells that did not express FcγRIIB1 and in splenic B cells treated with a FcγRII-specific mAb to block Fc binding. Internalization of monovalent Ag by B cells was reduced in the presence of whole anti-Ig as compared with F(ab′)2 anti-Ig, but the internalized Ag was correctly targeted to the class II peptide loading compartment. Taken together, these results indicate that the FcγRIIB1 is a negative regulator of the BCR-mediated Ag-processing function.