bluuebunny/crossref_metadata_2025_split huggingface dataset:
The human C‐type lectin CLECSF8 is a novel monocyte/macrophage endocytic receptor
Authors: Arce Ignacio , Martínez‐Muñoz Laura , Roda‐Navarro Pedro , Fernández‐Ruiz Elena 
Published: February 2004

AbstractCell surface lectin receptors play important roles in the function of macrophages. Herein, we have identified and characterized the human orthologue of the mouse Mcl/Clecsf8.Human CLECSF8 codes for a type II membrane glycoprotein of 215 amino acids that belongs to the human calcium‐dependent lectin family (C‐type lectin). The cytoplasmic tail of CLECSF8 lacks consensus signaling motifs and its extracellular region shows a single carbohydrate recognition domain (CRD). The CLECSF8 gene has been localized on the telomeric region of the NK gene complex on chromosome 12p13 close to MINCLE. CLECSF8 mRNA shows a monocyte/macrophage expression pattern. Biochemical analysis of CLECSF8 on transiently transfected cells showed a glycoprotein of 30 kDa. Cross‐linking of the receptor leads to a rapid internalization suggesting that CLECSF8 constitutes and endocytic receptor.See accompanying commentary http://dx.doi.org/10.1002/eji.200324641
CD4 T cells guarantee optimal competitive fitness of CD8 memory T cells
Authors: Johansen Pål , Stamou Panagiota , Tascon Ricardo E. , Lowrie Douglas B. , Stockinger Brigitta 
Published: February 2004

AbstractWe studied the contribution of CD4 T cell help to survival and competitive fitness of CD8 memory T cells specific for influenza virus nucleoprotein. In agreement with recent studies, the optimal generation of functional memory CD8 T cells required CD4 help, although long‐term maintenance of resting CD8 memory T cells did not absolutely depend on the presence of CD4 T cells. Nonetheless, CD4 T cells were essential during differentiation of CD8 memory T cells to imprint on them the capacity to compete effectively with other memory T cells. CD8 memory cells generated with help survived better in secondary polyclonal hosts, and co‐transfer into lymphopenic hosts together with "un‐helped" CD8 memory cells showed improved homeostatic expansion of CD8 memory cells that had been generated with CD4 help. Therefore, the requirement for CD4 help in CD8 T cell memory extends to homeostatic parameters that ensure the maintenance and competitive fitness of memory clones.
Antibody‐mediated bacterial clearance from the lower respiratory tract of mice requires complement component C3
Authors: Pishko Elizabeth J. , Kirimanjeswara Girish S. , Pilione Mylisa R. , Gopinathan Lakshmi , Kennett Mary J. , Harvill Eric T. 
Published: February 2004

AbstractTo assess the contribution of complement to respiratory immunity in the context of a natural bacterial infection, we used mice genetically deficient in complement components and the murine pathogen Bordetella bronchiseptica. Complement component C3 was not required for the control of bacterial infection or for the generation of infection‐induced protective immunity. However, C3‐deficient (C3–/–) mice were severely defective, compared to wild type, in vaccine‐induced protective immunity. Adoptively transferred immune serum from convalescent wild‐type or C3–/– animals rapidly cleared B. bronchiseptica from the lungs of wild‐type mice but did not affect its growth in C3–/– mice, indicating that the defect is not in the generation of protective immunity, but in its function. Immune serum was effective in C5‐deficient mice but had little effect in the lungs of mice lacking either Fcγ receptors (FcγR) or CR3, suggesting bacterial clearance is not via direct complement‐mediated lysis. Together, these data indicate that complement is required for antibody‐mediated clearance of Bordetella and suggest the mechanism involves C3 opsonization of bacteria for phagocytosis that is both CR3‐ and FcγR‐dependent.
Pulmonary tuberculosis in BALB/c mice with non‐functional IL‐4 genes: changes in the inflammatory effects of TNF‐α and in the regulation of fibrosis
Authors: Hernandez‐Pando Rogelio , Aguilar Diana , Hernandez Maria Luz Garcia , Orozco Hector , Rook Graham 
Published: February 2004

AbstractIn BALB/c mice, as in man, progressive pulmonary tuberculosis is accompanied by increasing expression of IL‐4. Therefore we have used BALB/c mice with disrupted IL‐4 genes (IL‐4–/–) to investigate the role of IL‐4 in pulmonary tuberculosis, with particular emphasis on the toxicity of TNF‐α and on fibrosis, both of which are neglected aspects of human tuberculosis. Delayed‐type hypersensitivity (DTH) sites in IL‐4+/+ mice were sensitive to the toxicity of locally injected TNF‐α, whereas DTH sites in IL‐4–/– mice were not. However, intravenous administration of IL‐4 to IL–4–/– mice restored the sensitivity of the DTH sites to pro‐inflammatory effects of TNF‐α. In late disease, the lungs of IL‐4+/+ mice expressed low IFN‐γ, but high TGF‐β and IL‐4, correlating with fibrosis, detected as a high hydroxyproline content. In contrast, TGF–β peaked 7 days after infection in the lungs of the IL‐4–/– mice, and then fell to very low levels in the late disease, while IFN‐γ remained high. Accordingly, hydroxyproline content was reduced in infected IL‐4–/– mice compared to IL‐4+/+ controls. In conclusion, the findings suggest that IL‐4 has modestly detrimental effects on the antibacterial efficacy of the Th1 response, and larger effects on the toxicity of TNF‐α, and on fibrosis.
Cross‐priming of CD8+ T cells by viral and tumor antigens is a robust phenomenon
Authors: Chen Weisan , Masterman Kelly‐Anne , Basta Sameh , Mansour Haeryfar S. M. , Dimopoulos Nektaria , Knowles Barbara , Bennink Jack R. , Yewdell Jonathan W. 
Published: February 2004

Abstract"Cross‐priming" refers to the activation of naive CD8+ T cells by antigen‐presenting cells that have acquired nominal antigens from another cell. The biological relevance of cross‐priming of CD8+ T cells has recently been challenged (Zinkernagel, R. M., Eur. J. Immunol. 2002. 32: 2385–2392), on the basis that responses are weak or poorly quantitated, and the determinants recognized are undefined. Here we show that cross‐priming is a robust process that elicits vigorous primary responses to multiple peptides in two well‐defined systems. Our findings support the relevance of cross‐priming in CD8+ T cell responses to viruses and tumor cells, and demonstrate that cross‐priming elicits CD8+ T cells to determinants generated by the endogenous processing pathway.
Arginase induction promotes Trypanosoma cruzi intracellular replication in Cruzipain‐treated J774 cells through the activation of multiple signaling pathways
Authors: Stempin Cinthia C. , Tanos Tamara B. , Coso Omar A. , Cerbán Fabio M. 
Published: February 2004

AbstractGiven that arginase activation may effectively influence nitric oxide (NO) production in macrophages, we have investigated the intracellular signals that regulate L‐arginine metabolism and its influence on Trypanosoma cruzi growth. We demonstrate that cruzipain (Cz), a parasite antigen, induces arginase I expression in J774 cells, and the pretreatment of Cz‐treated cells with N‐omega‐hydroxy‐L‐arginine (arginase inhibitor) leads to a dramatic decrease in amastigote growth. The study of intracellular signals shows that genistein [tyrosine kinase (TK) inhibitor], KT5720 [protein kinase (PK) A inhibitor] and SB203580 [p38 mitogen‐activated protein kinase (MAPK) inhibitor] significantly decrease Cz‐induced arginase activation. However, calphostin C (PKCinhibitor) and PD98059 [p44/p42 MAPK kinase (MEK) inhibitor] did not cause a significant change. To determine if signaling pathways triggered by Cz were involved in the T. cruzi growth, westudied the effect of those inhibitors. In Cz‐treated cells – pre‐incubated with TK, PKA or p38 MAPK inhibitors – the balance of NO/urea was biased towards NO, and the amastigote growth was diminished. Besides, genistein and mainly KT5720 induced down‐regulation of arginase I expression in Cz‐treated cells. Thus, activation of TK, PKA and p38 MAPK by Cz induces an increase of arginase activity in macrophages and the subsequent T. cruzi growth.
Drug‐induced autoantibody formation in mice: triggering by primed CD4+CD25– T cells, prevention by primed CD4+CD25+ T cells
Authors: Layland Laura E. , Wulferink Marty , Dierkes Sabine , Gleichmann Ernst 
Published: February 2004

AbstractAlthough the ability of CD4+CD25+ T suppressor (Ts) cells to prevent experimental autoimmune diseases has been described, nothing is known concerning their role and mechanismof action in xenobiotic‐induced autoimmunity. Procainamide, mercuric chloride, and gold(I) are three xenobiotics that can induce autoimmune reactions in humans and rodents. After the induction of IgG1 antinuclear autoantibodies (ANA) in mice treated with either of the above xenobiotics, adoptive transfer of their CD4+CD25+ T cells completely prevented ANA formation in recipients treated with the same xenobiotic; transfer of CD8+ T cells was ineffective. Furthermore, xenobiotic‐primed CD4+CD25+ T cells could also partially prevent ANA formation in recipients treated with a different xenobiotic. CD4+CD25– T cells from xenobiotic‐treated donors failed to suppress, but induced de novo IgG1 ANA formation in untreated recipients. Our findings suggest that during xenobiotic treatment T cell reactivity may spread from xenobiotic‐induced, nucleoprotein‐related neoantigens to peptides of the unaltered nucleoproteins.
Autoantibodies in autoimmune thyroid disease promote immune complex formation with self antigens and increase B cell and CD4+ T cell proliferation in response to self antigens
Authors: Nielsen Claus Henrik , Hegedüs Laszlo , Leslie Robert Graham Quinton 
Published: February 2004

AbstractB cells are centrally involved as antigen‐presenting cells in certain autoimmune diseases. To establish whether autoantibodies form immune complexes (IC) with self‐antigens in autoimmune thyroid disease (AITD) and promote B cell uptake of self‐antigen, sera from patients with Hashimoto's thyroiditis (HT), Graves' disease (GD) and healthy controls were incubated with human thyroglobulin (Tg) before adding normal peripheral blood mononuclear cells. The deposition of immunoglobulins and C3 fragments on B cells was then assessed. Inclusion of Tg in serum from HT patients promoted B cell capture of IgG and C3 fragments. Furthermore, the binding of Tg to B cells in preparations of normal blood cells was higher in HT serum than in serum from controls and correlated positively with the serum anti‐Tg activity, as did the B and CD4+ T cell proliferation. Disruption of the three‐dimensional structure of Tg by boiling reduced the proliferative responses. The dataindicate that anti‐Tg antibodies associated with AITD facilitate the formation of complement‐activating Tg/anti‐Tg complexes, binding of IC to B cells, and the subsequent proliferation of B and T cell subsets. This represents a novel mechanism for the maintenance of autoimmune processes in AITD and links autoreactive T cell responses with the presence of autoantibodies.
Dominance of CCL22 over CCL17 in induction of chemokine receptor CCR4 desensitization and internalization on human Th2 cells
Authors: Mariani Margherita , Lang Rosmarie , Binda Elisa , Panina‐Bordignon Paola , D'Ambrosio Daniele 
Published: February 2004

AbstractChemokines and their receptors play a pivotal role in controlling T cell trafficking in immunity and inflammation. Two chemokines, CCL17 and CCL22, activate the chemokine receptor CCR4, expressed on functionally distinct subsets of T cells: cutaneous leukocyte‐associated antigen (CLA)+ skin‐homing, T helper (Th) 2, and CD25+ T suppressor cells. Here, we compared the ability of CCL17 and CCL22 to promote CCR4 internalization as a mechanism of regulation of receptor function on human Th2 cells. We report that CCL22 is a potent and rapid inducer of CCR4 internalization, while CCL17 is not. CCR4 internalization does not require G protein coupling, while being dependent on lipid rafts integrity and clathrin‐coated pits functionality. Cell surface disappearance ofCCR4 is rapidly reversed upon removal of exogenous ligand by virtue of receptor recycling. CCR4 internalization leads to a loss of functional responsiveness, while recovery of surface expression leads to re‐acquisition of chemotactic sensitivity of Th2 cells. The differential CCR4 desensitization and internalization reported here and the distinct expression patterns of CCL17 and CCL22 observed in vivo suggest that while CCL17 may act first on CCR4 at the endothelial surface to promote vascular recognition, CCL22 could subsequently engage the receptor within the tissue microenvironmentto guide cellular localization.
Developmental status of CD4–CD8+ and CD4+CD8– thymocytes with medium expression of CD3
Authors: Sheard Michael A. , Liu Cunlan , Takahama Yousuke 
Published: February 2004

AbstractIn normal mice, more than 10% of thymocytes in the CD4+CD8– and CD4–CD8+ single‐positive (SP) subsets express a medium level of CD3 on the cell surface. However, the fate of CD3medium cells is unclear. The CD3medium SP subpopulations might contain (i) cells in an immature stage of the pathways leading to CD3high cells, (ii) cells in developmental pathways that do not lead to CD3high cells, or (iii) cells that have been negatively selected. We found that sorted CD3medium CD4+CD8– thymocytes from adult mice up‐regulated CD3 to high levels in reaggregation thymus organ culture. Unlike their CD3high counterparts, CD3medium CD4+CD8– thymocytes wereunable to undergo chemotaxis towards the chemokines CCL19 and CCL21. CD3medium thymocytes of both CD4+CD8– and CD4–CD8+ subsets were also considerably more responsive than CD3high SP cells to apoptotic signals induced in vitro by ligation of CD95 (Fas/APO‐1) or by dexamethasone. In both SP subsets, a higher frequency of thymocytes expressing forbidden Vβ+ T cell receptors reactive with endogenous mammary tumor virus superantigens was found in CD3medium subpopulations than in CD3high subpopulations.These findings argue that the CD3medium SP thymocyte subpopulations contain apoptosis‐susceptible precursor cells of CD3high SP cells and are subject to negatively selecting pressures.
Interleukin 10 regulates cell surface and soluble LIR‐2 (CD85d) expression on dendritic cells resulting in T cell hyporesponsiveness in vitro
Authors: Beinhauer Brigitte G. , McBride Jacqueline M. , Graf Philipp , Pursch Edith , Bongers Monique , Rogy Michael , Korthauer Ulf , de Vries Jan E. , Aversa Gregorio , Jung Thomas 
Published: February 2004

AbstractDendritic cells (DC) are unique in their ability to stimulate naive T cells to proliferate and to differentiate into effector T cells. DC, however, can also inhibit T cell activation and play a role in central and peripheral tolerance. IL‐10 has been shown to render DC tolerogenic by unknown mechanisms. Using a combined monoclonal antibody/retroviral expression cloning approach, we show here that the inhibitory receptor LIR‐2 (leukocyte immunoglobulin‐like receptor‐2, CD85d) is specifically up‐regulated by IL‐10 on maturing human DC. LPS‐stimulated, LIR‐2‐transfected DC inhibited the proliferation of T cells in autologous, as well as allogeneic culture systems in vitro. In addition, overexpression of LIR‐2 on resting T cells, which lack LIR‐2 expression, inhibited T cell proliferation induced by TCR activation. A novel soluble form of LIR‐2 was detected in culture supernatants of maturing DC. IL‐10 treatment of DC potently inhibited the production of soluble LIR‐2. Recombinant soluble LIR‐2 was able to completely restore the proliferation of T cells activated with LPS‐plus IL‐10‐treated DC. Thus, IL‐10 renders DC hypostimulatory by up‐regulating cell surface LIR‐2 and by inhibiting soluble LIR‐2 in vitro.
Dendritic cells generated in the presence of GM‐CSF plus IL‐15 prime potent CD8+ Tc1 responses in vivo
Authors: Pulendran Bali , Dillon Stephanie , Joseph Chryshanthi , Curiel Tyler , Banchereau Jacques , Mohamadzadeh Mansour 
Published: February 2004

AbstractDendritic cells (DC) comprise a system of professional antigen‐presenting cells, which induce the stimulation of very rare antigen‐specific naive T cells. DC progenitors can be stimulated to differentiate into immature DC by various growth factors, including GM‐CSF and IL‐4. Here we show that IL‐15, in combination with GM‐CSF, is a growth factor for murine DC. Murine bone marrow cells, depleted of T cells, B cells, I‐A+ cells and Gr‐1+ granulocytes, and cultured in the presence of GM‐CSF plus IL‐15 (IL‐15 DC), yielded DC expressing high levels of CD11c and MHC class II molecules, as well as CD11b. These cells expressed significant levels of CD40, CD80 and CD86, and could stimulate allogeneic CD4+ T cells efficiently. Interestingly, IL‐15 DC were farsuperior to DC generated with GM‐CSF plus IL‐4 in stimulating allogeneic CD8+ T cells in vitro. Consistent with this, IL‐15 DC induced much more potent antigen‐specific CD8+ T cell responses with high levels of Th1 cytokines in vivo, compared to DC generated with GM‐CSF plus IL‐4, or with GM‐CSF plus TGF‐β, or with GM‐CSF alone. Together, these data suggest that IL‐15 promotes the development of DC, which induce potent Th1 and Tc1 responses in vivo. This suggests potential roles for these IL‐15 DC cells in the immunotherapy of tumors and infectious diseases.
Identification of T cell epitopes on human proteolipid protein and induction of experimental autoimmune encephalomyelitis in HLA class II‐transgenic mice
Authors: Mangalam Ashutosh K. , Khare Meenakshi , Krco Christopher , Rodriguez Moses , David Chella 
Published: February 2004

AbstractMultiple sclerosis (MS) is an immune‐mediated demyelinating disease of the CNS that is associated with HLA class II molecules HLA‐DR2, ‐DR3 and ‐DR4. Previously, it has been difficult to analyze the role of individual HLA molecules in disease pathogenesis due to heterogeneity of MHC genes, linkage disequilibrium, influence of non‐MHC genes and contribution of environment. To overcome some of these problems, we have generated HLA‐transgenic (tg) mice to investigate function and interaction of these molecules in disease pathogenesis. To investigate the role of individual HLA class IIgenes in immune responses to human proteolipid protein (PLP), a candidate autoantigen in MS, mice expressing HLA genes DR2, DR3, DR4 (DRB1*;0401 and DRB1*;0402), DQ6 and DQ8, lacking endogenous class II molecules were immunized with overlapping peptides of PLP. In all tg mice, the majority of the dominant T cell epitopes were clustered mainly to three region; amino acids 31–70, 91–120 and 178–228, of the PLP molecules. We also identified an encephalitogenic epitope PLP91–110 that induced clinical EAE in HLA‐DR3 tg mice. These tg mice had inflammatory infiltrates classically associated with EAE and showed a Th1 cytokine profile. This humanized mouse model of MS will be valuable in deciphering the role of HLA molecules and autoantigens in MS.
The neuronal protein Kidins220 localizes in a raft compartment at the leading edge of motile immature dendritic cells
Authors: Riol‐Blanco Lorena , Iglesias Teresa , Sánchez‐Sánchez Noelia , de la Rosa Gonzalo , Sánchez‐Ruiloba Lucía , Cabrera‐Poch Noemi , Torres Ana , Longo Isabel , García‐Bordas Julio , Longo Natividad , Tejedor Alberto , Sánchez‐Mateos Paloma , Rodríguez‐Fernández José Luis 
Published: February 2004

AbstractKidins220, a protein predominantly expressed in neural tissues, is the first physiological substrate for protein kinase D (PKD). We show that Kidins220 is expressed in monocyte‐derived and in peripheral blood immature dendritic cells (im DC). Immature DC (im DC) migrate onto extracellular matrices changing cyclically from a highly polarized morphology (monopolar (MP) stage) to a morphologically symmetrical shape (bipolar (BP) stage). Kidins220 was localized on membrane protrusions at the leading edge or on both poles in MP and BP cells, respectively. CD43, CD44, ICAM‐3 and DC‐SIGN,and signaling molecules PKD, Arp2/3 were found at the leading edge in MP or on both edges in BP cells, showing an intriguing parallelism between morphology and localization of molecular components on the poles of the motile DC. F‐actin co‐localized and it was necessary for Kidins220 localization on the membrane in MP and BP cells. Kidins220 was also found in a raft compartment. Disruption of rafts with methyl‐β‐cyclodextrin induced rounding of the cells, inhibition of motility and lost of Kidins220 polarization. Our results describe for the first time the molecular components of the polesof motile im DC and indicate that a novel neuronal protein may be an important component among these molecules.
Commentary: C‐type lectins on the macrophage cell surface – recent findings
Authors: Marshall Andrew S. J. , Gordon Siamon 
Published: February 2004

AbstractInterest in the C‐type lectin family as a fundamental mediator of diverse immune interactions has grown exponentially in recent years, especially concerning members expressed on NK cells and their roles in anti‐viral and anti‐tumor immunity. For macrophages, however, collating the roles of the broad range of C‐type lectins expressed may be a more complex task. Analysis of the configuration of the C‐type lectin(‐like) domains among any other conserved modules reveals subfamilies of highly divergent structures. The identified ligands are likewise highly varied; however, most in vivo ligands are unknown and the significance of any recognized interactions is not well understood. In this commentary we review key features of C‐type lectin and lectin‐like receptor expression on macrophages and discuss recent data that sheds light on their varied functions. We aim to highlight the considerable body of novel/uncharacterized members of this receptor family and to place in context the initial description of CLECSF8, which is reported in this issue of the journal.See accompanying article http://dx.doi.org/10.1002/eji.200324230
The mitochondrial phase of the glucocorticoid‐induced apoptotic response in thymocytes comprises sequential activation of adenine nucleotide transporter (ANT)‐independent and ANT‐dependent events
Authors: Sade Hadassah , Khandre Nagamani S. , Mathew M. K. , Sarin Apurva 
Published: February 2004

AbstractIn thymocytes, dexamethasone initiates cytochrome c‐dependent processing of caspase‐9 and the activation of caspase‐3 to trigger apoptotic damage. Using murine thymocytes or a thymocyte cell line WEHI 7.1, we show that this pathway is inhibited by dominant‐negative caspase‐9, the anti‐apoptotic protein Bcl‐2, or by blocking components of the mitochondrial permeability transition pore complex (PTPC). We use DIDS (dithiocyanatostilbene‐2,2‐disulfonic acid), a pharmacological modifier of VDAC (voltage‐dependent anion channel) function or ectopic expression of hexokinase‐II, to examinethe role of the VDAC – a mitochondrial outer membrane protein – in this apoptotic pathway. This approach implicated the VDAC in dexamethasone‐mediated cytochrome c release, processing of caspase‐9 and caspase‐3, the loss of mitochondrial transmembrane potential (Δ ψm), nuclear damage and cell lysis. Inhibiting the adenine nucleotide transporter (ANT), a protein on the mitochondrial inner membrane, also blocks dexamethasone‐induced apoptosis, but the ANT regulates caspase‐3 processing and nuclear damage but not the mitochondrial efflux of cytochrome c. Collectively, the data identifytwo separable, but connected events in dexamethasone‐induced mitochondrial damage in thymocytes. The first event is an increase in permeability of the mitochondrial outer membrane leading to VDAC‐regulated efflux of cytochrome c and initial processing of caspase‐9 followed by ANT‐dependent caspase‐3 processing and apoptotic damage to cells.