bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of killer cell inhibitory receptors on human uterine natural killer cells
Authors: Verma Sanjay , King Ashley , Loke Yung Wai 
Published: March 2007

AbstractThe establishment of the human placenta in early pregnancy is characterized by the presence of large numbers of natural killer (NK) cells within the maternal decidua in close proximity to the fetally‐derived invading extravillous trophoblast which expresses at least two HLA class I molecules, HLA‐G and HLA‐C. These NK cells have an unusual phenotype, CD56bright CD16, distinguishing them from adult peripheral blood NK cells. They may control key events in trophoblast migration and therefore placentation. Human NK cells in peripheral blood express receptors for polymorphic HLA class I molecules. This family of receptors, known as killer cell inhibitory receptors (KIR), are expressed on overlapping subsets of NK cells to give an NK cell repertoire which differs between individuals. Using a panel of monoclonal antibodies to several members of the KIR family and analysis by flow cytometry, we have found that KIR are expressed by decidual NK cells. There is variation in both the percentage of cells expressing a particular receptor and the density of receptor expression between decidual NK cells from different individuals. Comparison of NK cells from decidua and peripheral blood of the same individual showed that NK cells from these two different locations express different repertoires of KIR. Receptors are present in individuals who do not possess the relevant class I ligand, raising the possibility that these NK receptors may be involved in recognition of the allogeneic fetus by the mother at the implantation site.
Up‐regulation of human epidermal Langerhans' cell B7‐1 and B7‐2 co‐stimulatory molecules in vivo by solar‐simulating irradiation
Authors: Laihia Jarmo K. , Jansen Christer T. 
Published: March 2007

AbstractUltraviolet (UV) radiation impairs cutaneous immune functions and induces antigen‐specific tolerance both locally at the irradiated skin site, as well as at distant skin sites and systemically. It has been postulated that in the local model, altered Langerhans' cells (LC) provide tolerogenic signals, and studies in vitro have indicated that UV radiation may down‐regulate the expression of co‐stimulatory molecules on the surface of these cells. To examine the effect of UV radiation on LC co‐stimulatory molecules in vivo, we irradiated human volunteers with erythematogenic doses of solar‐simulating UV radiation (SSR), and analyzed the expression of cell surface markers in dermatome skin samples obtained 1–72 h post‐irradiation. For flow cytometric analysis, epidermal cell (EC) suspensions were prepared and double labeled with monoclonal antibodies against CD1a or HLA‐DR, and B7‐1 (CD80), B7‐2 (CD86), ICAM‐1 (CD54), ICAM‐3 (CD50), LFA‐3 (CD58), E‐cadherin, or integrin‐β4 (CD104). In unirradiated control skin samples, keratinocytes (KC) expressed high levels of E‐cadherin. LC expressed high levels of both E‐cadherin and ICAM‐3, and low levels of B7‐2, LFA‐3, ICAM‐1, and integrin‐β4. Following SSR, a triphasic reaction pattern was seen: an immediate, down‐regulatory phase prevailing 2–6 h post‐irradiation, when the number of DR+ and CD1a+ cells were temporarily reduced; a delayed, up‐regulatory phase in which the number of LC was increased and the expression intensities of CD1a, HLA‐DR, B7‐1, and B7‐2 were strongly up‐regulated, maximally evident 12–24 h after irradiation, but no more seen at 48 h; and a late phase at 72 h, in which an influx of monocytes and a concomitant rise in DR+ cells was recorded. We conclude that to understand real‐life cutaneous UV immunology, studies in vitro need to be complemented with studies in vivo. In the case of LC, the effects of erythematogenic UV radiation in vivo on human LC B7 co‐stimulatory molecules include an up‐regulatory stage.
Deregulated TCRαβ T cell population provokes extramedullary hematopoiesis in mice deficient in the common γ chain
Authors: Sharara Lama I. , Andersson ÅSa , Guy‐Grand Delphine , Fischer Alain , Disanto James P. 
Published: March 2007

AbstractDeficiency of the cytokine receptor common γ chain (γc) results in abnormal lymphoid development and a severe immunodeficiency disease due to the combined loss of the receptors for interleukins (IL)‐2, ‐4, ‐7, ‐9, and ‐15. We have observed the development of secondary hematopoiesis with circulating hematopoietic progenitor cells in adult mice harboring a null mutation in γc. These extramedullary changes were not secondary to bone marrow failure or to an inability to maintain circulating blood counts. These results suggested that γc‐dependent cytokine signaling pathways modulate hematopoietic development. An intrinsic defect in γc− hematopoietic stem cell committment appeared unlikely, as fetal liver hematopoiesis was unaltered in γc− embryos. Furthermore, the absence of natural killer cells in γc− mice was not responsible for the observed hematopoietic changes. Peripheral TCRαβ T cells from γc− mice were characterized by an activated phenotype (CD62Llo, CD44hi, CD69hi) and showed increased levels of transcripts for hematopoietic stimulating cytokines, including IL‐3 and granulocyte/macrophage‐colony‐stimulating factor. A predominance of these cells was detected in the bone marrow, suggesting a role for residual T cells in the enhanced hematopoiesis. Strikingly, the elimination of residual T cells from γc− mice reduced splenic and circulating hematopoietic precursor frequencies to normal levels. These results clearly implicate a deregulated TCRαβ T cell population in the observed hematopoietic changes in γc− mice, and emphasize the importance of γc‐dependent cytokine interactions in modulating mature T cell responses.
Mice heterozygous for a deletion of the tumor necrosis factor‐α and lymphotoxin‐α genes: biological importance of a nonlinear response of tumor necrosis factor‐α to gene dosage
Authors: Amiot Franck , Boussadia Oréda , Cases Sylvaine , Fitting Catherine , Lebastard Mai , Cavaillon Jean‐Marc , Milon Geneviève , Dautry François 
Published: March 2007

AbstractThe tumor necrosis factors (TNF‐α and lymphotoxin, or LT‐α) are important mediators of the immune and inflammatory responses, and it has been proposed that a positive feedback loop could boost the expression of the TNF to sufficiently high levels to fend off infections. To investigate this phenomenon and its biological consequences, we have generated LT‐α/TNF‐α knockout mice and compared mice having one or two functional LT‐α/TNF‐α alleles. In response to lipopolysaccharide (LPS) stimulation, TNF‐α levels in the circulation or in the supernatant of macrophage cultures were 20‐ to 100‐fold lower in heterozygous samples than in their wild‐type counterparts. This differential increased with the intensity of stimulation and throughout the response, supporting the involvement of a positive feedback loop. Moreover, the heterozygous mice had an increased bacterial load following Listeria monocytogenes infection and exhibited a bimodal response to the association of D‐galactosamine and LPS which was similar to that of wild‐type mice at low doses of LPS and more like that of homozygous mutants at high doses. These results therefore establish the biological importance of the nonlinear response of TNF‐α levels to gene dosage, and these mice provide a unique tool to study how the propensity to produce TNF can determine the immunological fitness of individuals.
Insect venom immunotherapy induces interleukin‐10 production and a Th2‐to‐Th1 shift, and changes surface marker expression in venom‐allergic subjects
Authors: Bellinghausen Iris , Metz Gudrun , Enk Alexander H. , Christmann Steffen , Knop JÜRgen , Saloga Joachim 
Published: March 2007

AbstractThe current study was carried out to elucidate the immunoregulatory changes induced by venom immunotherapy (VIT) in bee or wasp allergic subjects. All subjects included in this study had a history of severe systemic allergic reactions to stings of the respective insect as well as positive skin tests with the respective venom or venom‐specific IgE in the sera. Parameters assessed in peripheral blood mononuclear cells (PBMC) before and after initiation of VIT (rush therapy reaching a maintenance dose of 100 μg venom injected subcutaneously within 1 week) were expression of CD3, CD4, CD8, CD45RA, CD45R0, interleukin (IL)‐2 receptor (R)α, IL‐4R, IL‐12R, FcσRII, CD40, and CD40 ligand (CD40L), cells producing interferon (IFN)‐γ and IL‐10 after stimulation with phorbol 12‐myristate 13‐acetate + ionomycin in the presence of monensin measured by flow cytometry; secretion of IFN‐γ, IL‐4, and IL‐10 measured by ELISA (IFN‐γ and IL‐10 were additionally measured by PCR), and proliferation after stimulation with the respective venom. Significant decreases were observed after VIT for proliferative response to venom and venom + IL‐4, IL‐4 secretion, FcσRII, CD40, and CD40L expression. Significant increases were observed after VIT for IFN‐γ concerning the amount secreted and the number of producing cells, and IL‐10. IL‐10 was mainly produced by CD4+ cells that were negative for IFN‐γ, but some double‐positive (IL‐10 and IFN‐γ) cells were always detected. Addition of blocking anti‐IL‐10 antibodies, but not isotype control antibodies, prevented down‐regulation of proliferation (but not IL‐4 secretion) and further enhanced IFN‐γ secretion after VIT. These data indicate that in insect venom allergic subjects, VIT not only induces a rapid shift in cytokine expression from Th2 to Th1 cytokines, but also leads to induction of the immunosuppressive cytokine IL‐10, which may be important for the limitation of potentially harmful allergen‐specific Th1 responses. The described changes in cytokine expression may be responsible for subsequent increases in allergen‐specific IgG and decreases in IgE production, as well as suppressive activity observed in earlier studies.
The human major histocompatibility complex class Ib molecule HLA‐E binds signal sequence‐derived peptides with primary anchor residues at positions 2 and 9
Authors: Braud Veronique , Yvonne Jones E. , McMichael Andrew 
Published: March 2007

AbstractHuman histocompatibility leukocyte antigen E (HLA‐E) and mouse major histocompatibility complex (MHC) class Ib antigen, Qa‐1, share the same substitutions at two normally conserved positions 143 and 147, which are likely to affect binding of the C terminus of peptides. Qa‐1 is able to bind a peptide derived from the leader sequence of H‐2 D and H‐2 L molecules. We developed a peptide binding assay in vitro to compare the binding specificity of HLA‐E with the mouse MHC class Ib molecule Qa‐1. We demonstrate that HLA‐E binds, although poorly, the peptide which binds to Qa‐1 and that it also binds nonamer signal sequence‐derived peptides from human MHC class I molecules. Using alanine and glycine substitutions, we could define primary anchor residues at positions 2 and 9 and secondary anchor residues at position 7 and possibly 3.
Stringent thiol‐mediated retention in B lymphocytes and Xenopus oocytes correlates with inefficient IgM polymerization
Authors: Carelli Stephana , Ceriotti Aldo , Sitia Roberto 
Published: March 2007

AbstractThiol‐dependent retention mechanisms involving the μs chain Cys575 ensure that only polymeric IgM are secreted. B lymphocytes are unable to polymerize IgM and degrade unpolymerized precursors intracellularly. Since several non‐lymphoid transfectants secrete hexameric IgM, specific mechanism(s) inhibiting IgM polymerization/secretion may be active in B cells. Here, we show that Xenopus laevis oocytes are also unable to polymerize IgM and retain this isotype via Cys575 as efficiently as B cells. The mechanisms and the hierarchy of the thiol‐dependent pre‐Golgi retention are conserved in amphibian oocytes, as indicated by the efficient retention of secretory IgA and the slow secretion of unassembled J558 λ chains. We also show that B cells do not lack any structural component necessary to polymerize IgM: after retention has been weakened by 2‐mercaptoethanol, polymerization can occur if oxidizing conditions are restored. Since release from retention can result in polymerization, stringent retention in B cells and oocytes might be at the basis of their common inability to polymerize secretory IgM. Our findings suggest that disulfide interchange reactions in the exocytic compartment can be modulated during B cell differentiation to control IgM secretion.
Diverse transcription factors are involved in the quantitative regulation of transcriptional activation of χ promoters
Authors: Bemark Mats , Leanderson Tomas 
Published: March 2007

AbstractImmunoglobulin χ promoters show sequence divergence but conserved function between different subgroups. Here we show that three separate 5′ elements are required for synergistic stimulation of transcription with the decamer in a χ promoter. These sites are a 5′ E‐box, a 3′ AT‐rich region in the pentadecamer (pd) element, and the χ‐Y element. Elf‐1 is a novel χ‐Y element ligand induced upon mitogenic stimulation of resting B lymphocytes. Furthermore, the 5′ E2A‐like E‐box in the pd element could be substituted by an upstream stimulatory factor motif with conservation of function. Thus, the synergistic activation requirements of χ transcription is strictly dependent on the quantitative presence of transcription factor‐binding motifs 5′ of the decamer, but these differ qualitatively in that they may bind an array of proteins with conserved function.
Induction of CD4+ T cell depletion in mice doubly transgenic for HIV gp120 and human CD4
Authors: Finco Oretta , Nuti Sandra , de Magistris Maria Teresa , Mangiavacchi Lucia , Aiuti Alessandro , Forte Pietro , Fantoni Antonio , Putten Herman Van Der , Abrignani Sergio 
Published: March 2007

AbstractIt has been suggested that loss of uninfected T cells in HIV infection occurs because of lymphocyte activation resulting in cell death by apoptosis. To address the question of whether cross‐linking of CD4/HIV gp120 complexes by antibodies were sufficient to induce T cell depletion in vivo, we developed an animal model of continuous interaction between human CD4 (hCD4), gp120 and anti‐gp120 antibodies in the absence of other viral factors. Double‐transgenic mice have been generated in which T cells express on their membrane hCD4 and secrete HIV gp120. Although these mice have hCD4/gp120 complexes present on the surface of T cells, they do not show gross immunological abnormalities, and they are able to produce anti‐gp120 antibodies following immunization with denaturated gp120. However, double‐transgenic mice with antibodies to gp120, when immunized with tetanus toxoid, mount an IgG response that is significantly lower than that of double‐transgenic mice without antibodies to gp120. Furthermore, the presence of anti‐gp120 antibodies leads to CD4+ T cell depletion and immunodeficiency in the absence of HIV infection. Thus, the antibody response to gp120 can lead to CD4+ T cell attrition in vivo.
HTLV‐I‐infected T cells activate autologous CD4+ T cells susceptible to HTLV‐I infection in a co‐stimulatory molecule‐dependent fashion
Authors: Takamoto Tetsuro , Makino Masahiko , Azuma Miyuki , Kanzaki Tamotsu , Baba Masanori , Sonoda Shunro 
Published: March 2007

AbstractA vigorous production of human T lymphotropic virus type I (HTLV‐I)‐infected CD4+ T cells is closely associated with the development of adult T cell leukemia (ATL) and neurological disease. However, the immunological mechanisms leading to generation of the HTLV‐I‐infected cells are not fully clarified. The modulation of CD80 and CD86 expression on the HTLV‐I‐infected cells and its physiological role in the interaction of infected CD4+ T cells with uninfected CD4+ T cells was examined. The HTLV‐I‐infected CD4+ T cell lines established from ATL patients and normal donors by infecting their CD4+ T cells with the virus expressed CD80, CD86, and HLA‐DR, and induced a proliferation of autologous and allogenic CD4+ T cells. While the CD4+ T cells stimulated with the autologous HTLV‐I‐infected cells for 7 days expressed CD80 and CD86 but not HTLV‐I gene products, they expressed HTLV‐I gag antigen after 4 weeks. The interaction of HTLV‐I‐infected and ‐uninfected CD4+ T cells was profoundly suppressed by a combination of CD80 and CD86 monoclonal antibodies. These results suggest that the induction of CD80 and CD86 on HTLV‐I‐infected CD4+ T cells participates actively in the generation of the virus‐infected progenitor cells.
Identification of epitopes on a mutant form of Pseudomonas exotoxin using serum from humans treated with Pseudomonas exotoxin containing immunotoxins
Authors: Roscoe Donna M. , Pai Lee H. , Pastan Ira 
Published: March 2007

AbstractPE38 is a 38‐kDa derivative of the 66‐kDa Pseudomonas exotoxin (PE) in which the cell binding domain of PE (domain Ia, amino acids 1–252) and a portion of domain Ib (amino acids 365–380) are deleted. The immunotoxins LMB‐1 and LMB‐7 contain PE38 and kill cancer cells by exploiting the cytotoxic action of PE38. The major human B cell epitopes of PE38 were mapped by measuring the reactivity of 45 serum samples from patients treated with the PE38‐containing immunotoxins LMB‐1 or LMB‐7 to two panels of overlapping synthetic peptides representing the sequence of PE38. One panel of peptides is ten amino acids long and overlap by seven amino acids, and the second panel of peptides is twenty amino acids long and overlap by ten. Five major epitopes were identified: amino acids 274–283, 470–492, 531–540, 555–564, and the C‐terminal amino acids 596–609. Two minor epitopes were identified as well: amino acids 501–510 and 582–589. These epitopes are predominantly located on the surface of the protein. The amino acids believed to be critical for binding are highly solvent‐accessible residues. The results of the human antibody response to peptides are compared to the pattern of reactivity previously identified with serum samples obtained from monkeys administered LMB‐1 and LMB‐7. The epitopes between monkey and human are almost identical, demonstrating similarity in the response of antibody repertoires between the two species and providing further support that these are the immunodominant epitopes. This information is critical for genetically engineering less immunogenic immunotoxins and provides a foundation for the development of a vaccine against pseudomonal infections which plague immunocompromised individuals and individuals with cystic fibrosis.
The role of E‐ and P‐selectin in neutrophil and monocyte migration in adjuvant‐induced arthritis in the rat
Authors: Walter Ulrike M. , Issekutz Andrew C. 
Published: March 2007

AbstractThe role of the endothelial adhesion molecules E‐ and P‐selectin in leukocyte accumulation in arthritis is not known. We investigated this role in rat adjuvant arthritis by employing adhesion function‐blocking monoclonal antibodies (mAb) to rat P‐ and E‐selectin. The acute migration (2 h) of radiolabeled rat blood neutrophils and monocytes to joints and skin was determined. Anti‐P‐selectin mAb significantly reduced accumulation of monocytes (by 50%) and neutrophils (by 40%) in the talar joint, and of neutrophils in tail joints (by 90%). Anti‐E‐selectin mAb alone did not attenuate leukocyte migration, but when combined with anti‐P‐selectin mAb, it enhanced inhibition of neutrophil accumulation in the talar and carpal joints. In the same animals, anti‐P‐selectin mAb significantly inhibited neutrophil and monocyte migration to dermal inflammatory reactions induced by zymosan‐activated rat serum (ZAS) containing the chemotactic factor C5ades Arg, endotoxin (LPS), interferon‐γ (IFN‐γ) and tumor necrosis factor‐α (TNF‐α). In contrast, anti‐E‐selectin mAb alone had no effect on monocyte or neutrophil accumulation in inflamed skin of arthritic animals, but again enhanced the inhibition when combined with mAb to P‐selectin. The addition of anti‐L‐selectin mAb to anti‐P‐ and E‐selectin mAb did not further suppress monocyte or neutrophil migration to inflamed skin or joints. These results demonstrate that optimal leukocyte migration to arthritic joints and inflamed skin is P‐selectin dependent, and E‐selectin is not essential. However, E‐selectin contributes to migration when P‐selectin mechanisms are not operative. L‐selectin does not play a role in E‐ and P‐selectin‐independent leukocyte migration to joints or skin inflammation in arthritic rats. However, it is likely that additional selectin‐independent pathways also mediate neutrophil and monocyte migration to joint and skin inflammation.
Cytokine responses induced by Toxoplasma gondii in astrocytes and microglial cells
Authors: Fischer Hans‐Georg , Nitzgen Bernd , Reichmann Gaby , Hadding Ulrich 
Published: March 2007

AbstractTo investigate the role of astroglia in intracerebral immune response to Toxoplasma gondii, astrocytes cultured from mouse brain were inoculated with mouse‐virulent or ‐avirulent toxoplasma strains. In comparison to microglia/brain macrophages, astrocytes as host cells allowed stronger proliferation of avirulent parasites. Toxoplasma infection of astroglia was accompanied by release of interleukin‐ (IL)1α, IL‐6, and granulocyte/macrophage colony‐stimulating factor (GM‐CSF) activity, whereas alternative challenge by lipopolysaccharide (LPS) evoked no IL‐1 response and significantly higher titers of IL‐6 and GM‐CSF. At the mRNA level, both stimuli induced transcription of all three cytokines in astrocytes. Secretion of IL‐1 and IL‐6 upon infection was triggered by T. gondii brady‐ and tachyzoites in a time‐ and dose‐dependent manner. Heat killing of parasites, but not an exposure to polymyxin B, abrogated their cytokine‐inducing activity, thus indicating that an LPS‐independent stimulus is provided by T. gondii. When administered in combination, LPS synergistically augmented the IL‐1‐inducing effect of toxoplasma infection. In comparison, T. gondii‐induced, but not an LPS‐triggered, IL‐6 response of astrocytes resisted to antagonization with IL‐10. The IL‐6 response of parasitized astroglia was up‐regulated by external tumor necrosis factor (TNF)‐α and transforming growth factor (TGF)‐β1, with only TNF‐α enhancing simultaneous release of IL‐1. Substantial secretion of IL‐10 and TNF‐α was detected in T. gondii‐infected microglia, but not in astrocyte cultures. A possibly autocrine stimulation of infected astroglia via IL‐1 was found to be unlikely, since addition of IL‐1 receptor antagonist did not affect the release of IL‐6 and GM‐CSF while inhibiting these responses in IL‐1‐treated cells. The findings substantiate a separate, T. gondii‐induced pathway of astroglia activation characterized by the release of IL‐1 which may drive local inflammatory reaction both at initial infection of the brain and during reactivating toxoplasmosis.
Prevention of endotoxin‐induced lethality in neonatal mice by interleukin‐13
Authors: Nicoletti Ferdinando , Mancuso Giuseppe , Cusumano Vitaliano , Marco Roberto Di , Zaccone Paola , Bendtzen Klaus , Teti Giuseppe 
Published: March 2007

AbstractInterleukin(IL)‐13, a cytokine produced by T helper 2 (Th2) cells, is a powerful inhibitor of macrophage functions, including surface expression of CD14 and production of IL‐1 and tumor necrosis factor (TNF)‐α. We tested the effects of recombinant mouse(m)IL‐13 in a neonatal mouse model of endotoxin shock; this is a macrophage‐dependent condition, which is a model of neonatal sepsis in humans. mIL‐13 (0.5 μg/mouse) dramatically reduced the lethal effects of lipopolysaccharide (LPS) if administered either 24 or 4 h prior to or concomitantly with LPS challenge. This action might be mediated by multiple modulatory activities of IL‐13 on LPS‐induced cytokine secretion since, relative to control animals, the mice treated with mIL‐13 had eight times lower peak blood levels of TNF. The IL‐1β levels were also decreased, whereas increased levels of IL‐6 and IL‐10 were observed at several time points after LPS challenge.