bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rat bone marrow‐derived dendritic cells, but not ex vivo dendritic cells, secrete nitric oxide and can inhibit T‐cell proliferation
Authors: Powell Timothy J. , Jenkins Chris D. , Hattori Ryuichi , MacPherson G. Gordon 
Published: May 2003

SummaryThe relationships between different dendritic cell (DC) populations are not clearly established. In particular, it is not known how DC generated in vitro relate to those identified in vivo. Here we have characterized rat bone marrow‐derived DC (BMDC) and compared them with DC isolated from spleen (SDC) and pseudo‐afferent lymph (LDC). BMDC express typical DC markers and are mostly OX41 positive and CD4 negative. In contrast to ex vivo DC, some BMDC express Fc receptors. FcR+ and FcR− BMDC express similar levels of major histocompatibility complex class II molecules (MHC) and are B7 positive, but some FcR− BMDC express high levels of B7. In contrast to freshly isolated or cultured ex vivo SDC and LDC, both BMDC subpopulations can express inducible nitric oxide synthase (iNOS) and can secrete nitric oxide (NO) in amounts similar to those secreted by peritoneal macrophages. Despite expressing MHC class II and B7, FcR+ BMDC stimulate only a very weak MLR and inhibit stimulation by FcR− BMDC and ex vivo DC. Inhibition is only partially NO dependent. FcR+ BMDC are not macrophages, as judged by adherence and phagocytosis. Both subpopulations are able to present antigen to primed T cells in vitro and are able to prime naïve CD4 T cells in vivo. However, unlike SDC, BMDC are unable to stimulate cytotoxic T‐lymphocyte (CTL) responses to a minor histocompatibility antigen. Thus, BMDC show marked differences to ex vivo DC and their relationship to those of in vivo DC populations, to date, is unclear.
Analysis of differential immune responses induced by innate and adaptive immunity following transplantation
Authors: He Hongzhen , Stone James R. , Perkins David L. 
Published: May 2003

SummaryThe roles of innate and adaptive immunity in allograft rejection remain incompletely understood. Previous studies analysing lymphocyte deficient or syngeneic graft recipients have identified subsets of inflammatory chemokines and cytokines induced by antigen independent mechanisms. In the current study, we analysed a panel of 60 inflammatory parameters including serum cytokines, intragraft chemokines and cytokines, receptors, and cellular markers. Our results confirmed the up‐regulation of a subset of markers by innate mechanisms and also identified a subset of parameters up‐regulated only in the context of an adaptive response. Thus, we successfully differentiated markers of the innate and adaptive phases of rejection. Current paradigms emphasize that innate signals can promote a subsequent adaptive response. Interestingly, in our studies, expression of the markers induced by innate mechanisms was markedly amplified in the allogeneic, but not syngeneic or lymphocyte deficient, recipients. These results suggest that inflammatory mediators can have functional overlap between the innate and adaptive responses, and that the adaptive component of the rejection process amplifies the innate response by positive feedback regulation.
Isolation of proliferation factor of immature T‐cell clone in concanavalin A‐stimulated splenocyte culture supernatant
Authors: Kohama Yasuhiro , Shinoda Shinji , Hagihara Katsunobu , Hashimoto Takeshi , Yamaguchi Asuka , Nakamura Akihiro , Tsuchiya Takahiro , Tsujikawa Kazutake , Yamamoto Hiroshi 
Published: May 2003

SummaryAn athymic mouse‐derived immature T‐cell clone, N‐9F, was not maintained by interleukin‐2 alone but required another soluble factor, contained in concanavalin A‐stimulated rat splenocyte culture supernatant, namely T cell growth factor (TCGF), for its proliferation. An N‐9F‐proliferation factor (NPF) was isolated in a pure form from TCGF. N‐9F cells and immature thymocytes proliferated in the presence of NPF at 10−11−10−8 g/ml in a dose‐dependent manner, but adult thymocytes were not stimulated by NPF. NPF increased DNA synthesis of N‐9F. NPF increased CD4 and CD8 double negative thymocytes and CD8 single positive thymocytes in fetal thymus organ culture. A hamster anti‐NPF antiserum possessing the capacity to neutralize N‐9F proliferation activity of NPF decreased double negative thymocytes. The amino‐terminal amino acid sequence of NPF was identified to be Ser‐Leu‐Pro‐Cys‐Asp‐Ile‐Cys‐Lys‐Thr‐Val‐Val‐Thr‐Glu‐Ala‐Cys‐Asn‐Leu‐Leu‐Lys‐Asp‐ and was identical to that of rat saposin A. The apparent molecular weight of NPF, 16 000, was comparable to that of saposin A. A rabbit anti‐mouse recombinant His‐tag (mrH)‐saposin A antibody recognized a 16 000 MW molecule in TCGF. A Hitrap‐saposin A antibody column bound NPF and pulled down the NPF activity in TCGF. Thus, NPF in TCGF was a saposin A‐like protein possessing the capacity for growth and differentiation of immature thymocytes.
Infection with chicken anaemia virus impairs the generation of pathogen‐specific cytotoxic T lymphocytes
Authors: Markowski‐Grimsrud Carrie J. , Schat Karel A. 
Published: May 2003

SummaryInfection with chicken anaemia virus (CAV), a circovirus, can result in immunosuppression and subsequent increased susceptibility to secondary infections. This is the first report of impairment of pathogen‐specific cytotoxic T lymphocytes (CTL) after natural and experimental infection of chickens with CAV and Marek's disease virus (MDV) or reticuloendotheliosis virus (REV). MDV‐ and REV‐specific CTL were generated at 7 days post infection by 9–30‐day‐old‐chickens that were positive for maternal antibodies to CAV at 9–17 days of age. Replication of CAV could not be demonstrated in these chickens using quantitative real‐time polymerase chain reaction (PCR) and reverse transcriptase (RT)–PCR assays. In contrast, REV‐specific CTL failed to develop when chickens negative for maternal antibodies at 9–17 days of age were infected. Infection with CAV at 45 days of age after CAV maternal antibodies had waned also caused a decreased REV‐specific CTL response. In these chickens increased levels of CAV DNA of up to 107 copy numbers per µg DNA and increased relative transcript levels of CAV by up to a factor of 106 were detected by quantitative real‐time PCR and RT–PCR. Interleukin (IL)‐1β and IL‐2 mRNA levels were not significantly affected by CAV infection at 7 or 14 days p.i. Similar assays for interferon‐γ (IFN‐γ) transcripts demonstrated a 10‐fold increase in IFN‐γ mRNA levels at 7 days post infection following REV or REV + CAV infection, while CAV alone caused a two‐ to fourfold increase. These results show a strong link between CAV antibody status, CAV replication, and the ability to generate REV‐specific CTL. It is likely that the immunosuppressive effects of subclinical infection have previously been underestimated.
Assessment of oral transmission using cell‐free human immunodeficiency virus‐1 in mice reconstituted with human peripheral blood leucocyte
Authors: Nakao Ryoma , Hanada Nobuhiro , Asano Toshihiko , Hara Takashi , Abdus Salam Md , Matin Khairul , Shimazu Yoshihito , Nakasone Tadashi , Horibata Shigeo , Aoba Takaaki , Honda Mitsuo , Amagasa Teruo , Senpuku Hidenobu 
Published: May 2003

SummaryOral–genital contact is one of the risk factors for the transmission of human immunodeficiency virus (HIV) in adults. In recent reports, oral exposure to simian immunodeficiency virus (SIV) was found to have important implications for the achievement of mucosal transmission of HIV in a rhesus monkey animal model. In the present study, we aimed first to establish a small animal model which did not develop tonsils suitable for HIV oral mucosa transmission, using non‐obese diabetic/severe combined immunodeficiency (NOD/SCID) mice and NOD/SCID B2mnull mice grafted with human peripheral blood leucocytes (hu‐PBL) and stimulated with interleukin (IL)‐4, and second to investigate whether oral exposure to cell‐free R5 and X4 HIV‐1 could lead to oral transmission of HIV through intact or traumatized mucosal tissues in humanized mice. Both low and high concentrations of cell‐free R5 and X4 viruses failed to cause oral transmission with or without trauma in hu‐PBL‐NOD/SCID and NOD/SCID Β2mnull mice, which presented a number of CD4+ cells in gingival tissues and oral cavities with or without tissue injury. The present results show that IL‐4‐administrated NOD/SCID B2mnull mice are useful as a small‐humanized model for the study of HIV oral infection, which may help to define the window of opportunity for oral transmission by the HIV virus in animal model experiments.
Increased interleukin‐10 expression is not responsible for failure of T helper 1 immunity to resolve airborne Mycobacterium tuberculosis infection in mice
Authors: Jung Yu‐Jin , Ryan Lynn , LaCourse Ronald , North Robert J. 
Published: May 2003

SummaryWith a view to determining whether failure of mice to resolve Mycobacterium tuberculosis (Mtb) infection is a consequence of downregulation of T helper 1 (Th1) immunity by interleukin (IL)‐10, mice deleted of the gene for IL‐10 were compared with wild‐type (WT) mice in terms of their ability to make IL‐10 mRNA, generate Th1‐mediated immunity [as measured by synthesis of mRNA for interferon‐γ (IFN‐γ)], IL‐12p40 and inducible nitric oxide synthase (iNOS), and to control lung infection. It was found that the response of WT mice to infection included a substantial and sustained increase in IL‐10 mRNA synthesis in the lungs. A Th1 response in the lungs of WT and IL‐10−/− mice was evidenced by a large and sustained increase in the synthesis of mRNA for IFN‐γ, IL‐12p40 and iNOS, with somewhat higher levels of these mRNA species being made in the lungs of IL‐10−/− mice, particularly at an early stage of infection. However, IL‐10−/− mice were no more capable than WT mice at combating infection.
Age‐related increase of peripheral CD4+ CD8+ double‐positive T lymphocytes in cynomolgus monkeys: longitudinal study in relation to thymic involution
Authors: Lee Won‐Woo , Nam Ki‐Hoan , Terao Keiji , Akari Hirofumi , Yoshikawa Yasuhiro 
Published: May 2003

SummaryThe age‐related increase of peripheral CD4+ CD8+ double‐positive (DP) T cells in cynomolgus monkeys has been reported previously. Because the percentage of DP T cells in cynomolgus monkeys increases abruptly in parallel with the thymic involution occurring at around 11 years of age, it was suggested that thymic involution was associated with this increase. Therefore, a longitudinal study was carried out over 5 years to clarify the exact time when DP T lymphocytes start to increase in relation to the thymic involution. Twelve cynomolgus monkeys at 6 years of age were classified into three groups, based on their percentage of DP T cells, as follows: DP‐High (>5% DP T cells); DP‐Middle (1–5% DP T cells); and DP‐Low (<1% DP T cells). In the DP‐High group, the percentage of DP T cells showed an abrupt increase, of >10%, in monkeys at 7 years of age, and the prevalence of this subset correlated with a distinctive increase in the percentage of memory T cells (CD4+ CD29high, CD8+ CD28−), indicating an association with the maturation of immune function, including thymic involution. To assess the thymic function, the coding joint of T‐cell receptor excision circles (cjTREC) levels in sorted T cells were analysed by polymerase chain reaction (PCR)‐enzyme‐linked immunosorbent assay (ELISA). The cjTREC in the T cells of the DP‐High group (4362 ± 3139 copies/105 T cells) was significantly lower than that (22 722 ± 4928 copies/105 T cells) of the DP‐Low group. Moreover, the mean copy number of cjTREC in naive T cells was also significantly different between the DP‐High and the DP‐Low group (0·457 ± 0·181 and 1·141 ± 0·107, respectively). These findings suggest that thymic involution has an influence on the age‐related increase of DP T cells in cynomolgus monkeys.
NIM‐R7, a novel marker for resting B1 and marginal‐zone B lymphocytes, is also expressed on activated T and B cells
Authors: Manjarrez‐Orduño Nataly , Parkhouse R Michael E. , Santos‐Argumedo Leopoldo 
Published: May 2003

SummaryIn mice, follicular B cells have been studied in detail, while two other B‐cell subpopulations – marginal‐zone B and B1 cells – are less well understood. In this work we report the expression pattern of p58, a lymphocyte‐activation marker, recognized by rat monoclonal antibody, NIM‐R7, and present on the latter two cell subpopulations. Staining with NIM‐R7 showed that undisturbed marginal‐zone B cells, as well as peritoneal cavity and splenic B1a cells, constitutively expressed p58, whereas follicular B cells and resting T lymphocytes did not. Ontogenic analysis of different compartments showed that p58 did not appear at any stage of development, prior to the development of mature T or B2 lymphocytes. Upon polyclonal stimulation, however, p58 appeared on both T and B2 lymphocytes. Finally, ricin A‐conjugated NIM‐R7 was able to kill the BCL1 lymphoma without effect on mature resting B2 cells. Therefore, p58 may be a potential target for diagnosis or therapy of B1 and marginal‐zone B‐cell malignancies.
Costimulation through OX40 is crucial for induction of an alloreactive human T‐cell response
Authors: Ukyo Naoya , Hori Toshiyuki , Yanagita Soshi , Ishikawa Takayuki , Uchiyama Takashi 
Published: May 2003

SummaryThe alloreactive immune response is a series of events initiated by the interaction of T cells with allogeneic dendritic cells (DCs), involving alloantigen recognition and costimulatory signals. In this study, we investigated the role of OX40 in alloreactivity in vitro. We first demonstrated that anti‐OX40 ligand (anti‐OX40L) monoclonal antibody (mAb) could markedly suppress the mixed leucocyte reaction (MLR) of peripheral blood mononuclear cells (PBMC). To further define the contribution of the OX40/OX40L system to the MLR, we set up a co‐culture system of CD4+ T cells and allogeneic monocyte‐derived dendritic cells (DCs). After 2 days, OX40 expression was induced on CD4+ T cells and this induction was strongly inhibited by the addition of cytotoxic T lymphocyte‐associated antigen‐4 (CTLA‐4)–Fc fusion protein, suggesting that the expression of OX40 during alloreaction is dependent on CD28 signalling. Next we examined the effects of anti‐OX40L mAb, CTLA‐4–Fc fusion protein and anti‐human leucocyte antigen (HLA)‐DR mAb on the proliferative response of CD4+ T cells to allogeneic DCs. The proliferation of T cells was almost completely suppressed by anti‐OX40L mAb, which was comparable with that of CTLA‐4–Fc. Measurement of interleukin‐2 (IL‐2) production in the culture supernatants showed that suppression of a proliferative response was at least in part ascribed to reduced IL‐2 production. Furthermore, purified OX40L− allogeneic DCs could induce considerable proliferation of CD4+ T cells, which was suppressed by anti‐OX40L mAb. These results suggest that the OX40/OX40L system is crucial for induction of the allogeneic T‐cell response and the OX40/OX40L system is subsequent to and dependent on CD28 signalling, but is crucial for the end outcome of the human alloreactive T‐cell response.
Soluble FcγRIIa inhibits rheumatoid factor binding to immune complexes
Authors: Wines Bruce D. , Gavin Amanda , Powell Maree S. , Steinitz Michael , Buchanan Russell R. C. , Mark Hogarth P. 
Published: May 2003

SummarySoluble low‐affinity receptors for IgG are known to inhibit immune complex (IC)‐mediated inflammation, and expression by leukocytes is elevated in several inflammatory diseases. Immunoglobulin M (IgM) rheumatoid factors (RF), anti‐Fc autoantibodies, are found in autoimmune diseases, such as rheumatoid arthritis (RA), as well as in normal immune responses. This study demonstrated that soluble FcγRIIa inhibits the interaction of rheumatoid factors with ICs. The recombinant soluble low‐affinity FcγR, rsFcγRIIa, partially inhibited (30–70%) the rate of precipitation of soluble ICs by RF‐positive RA sera. This required the normal interaction of FcγRIIa with Fc as the effect could be abrogated with the Fab fragment of the blocking mAb IV‐3. Furthermore, rsFcγRIIa partially inhibited (40%) the binding of a monoclonal IgM RF (RF‐AN) to an IC formed by IgG2 antibody binding to an antigen‐coated biosensor chip. Since RF‐AN has been characterized by crystallography to bind to the CH2/CH3 interface of the IgG‐Fc, and leukocyte FcγRIIa binds to a distinct site centred on the lower hinge, this inhibition is uncompetitive. Some inhibition (15%) of staphylococcal protein A binding to IC was also observed. As soluble FcγRIIa disrupts Fc:Fc interactions in IgG‐ICs, we propose that this alteration of the IC also reduces the accessibility of Fc portions in the IC, resulting in the partial inhibition of ligands, particularly IgM RF, which bind Fc. We propose that the high concentrations of soluble FcγR found during inflammation can affect the properties of ICs and their interaction with the immune system.
Effect of cytofectins on the immune response of murine macrophages to mammalian DNA
Authors: Zhu Fu‐Gang , Reich Charles F. , Pisetsky David S. 
Published: May 2003

SummaryDNA, depending on base sequence, can induce a wide range of immune responses. While bacterial DNA is stimulatory, mammalian DNA is inactive alone and can, moreover, inhibit the response to bacterial DNA. To determine whether the mode of cell entry affects the immune properties of mammalian DNA, we have investigated the effects of the cytofectin agents Fugene 6 (Roche Diagnostics Corp., Indianapolis, IN), Lipofectin and Lipofectamine (Life Technologies, Grand Island, NY) on the responses of murine macrophages to DNA from calf thymus and human placenta. Whereas calf thymus and human placenta DNA alone failed to stimulate J774 or RAW264·7 cell lines or bone marrow‐derived macrophages, these DNAs in complexes with cytofectin agents stimulated macrophages to produce nitric oxide but not interleukin 12. Both single‐stranded and double‐stranded DNAs were active in the presence of cytofectins. Macrophage activation by the DNA–cytofectin complexes was reduced by chloroquine, suggesting a role of endosomal acidification in activation. As shown by flow cytometry and confocal microscopy, the cytofectins caused an increase in the uptake of DNA into cells. Our findings indicate that macrophages vary in their response to DNA depending on uptake pathway, suggesting that activation by DNA reflects not only sequence but also context or intracellular location.
Immunotherapy of spontaneous mammary carcinoma with fusions of dendritic cells and mucin 1‐positive carcinoma cells
Authors: Chen Dongshu , Xia Jianchuan , Tanaka Yasuhiro , Chen Hongsong , Koido Shigeo , Wernet Oliver , Mukherjee Pinku , Gendler Sandra J. , Kufe Donald , Gong Jianlin 
Published: May 2003

SummaryThe tumour‐associated antigen mucin 1 (MUC1) is a multifunctional protein involved in protection of mucous membranes, signal transduction, and modulation of the immune system. More than 70% of cancers overexpress MUC1, making MUC1 a potential target for immunotherapy. In the present study, MUC1 transgenic mice were crossed with syngeneic strains that express the polyomavirus middle‐T oncogene (PyMT) driven by the mouse mammary tumour virus promoter long‐terminal repeat (MMTV‐LTR). The resultant breed (MMT mice) developed spontaneous MUC1‐expressing mammary carcinomas with 100% penetrance at 8–15 weeks of age. As found in human breast cancer, the mammary carcinoma in MMT mice arose in multiple stages. Immunization with fusions of dendritic cells and MUC1‐positive tumour cells (FC/MUC1) induced MUC1‐specific immune responses that blocked or delayed the development of spontaneous breast carcinomas. In contrast, there was no delay of tumour development in MMT mice immunized with irradiated MC38/MUC1 tumour cells. The efficacy of fusion cells was closely correlated with the timing of initial immunization. Immunization with FC/MUC1 initiated in MMT mice at < 1, 1–2 and 2–3 months of age rendered 33, 5 and 0% of mice free of tumour, respectively, up to 6 months. Whereas mice immunized in the later stage of tumour development succumbed to their disease, immunization resulted in control of tumour progression and prolongation of life. These results indicate that immunization with FC/MUC1 can generate an anti‐MUC1 response that is sufficient to delay the development of spontaneous mammary carcinomas and control tumour progression in MMT mice.
Innate self recognition by an invariant, rearranged T‐cell receptor and its immune consequences
Authors: Stanic Aleksandar K. , Park Jang‐June , Joyce Sebastian 
Published: May 2003

SummaryThis review attempts to illuminate the glycolipid antigen presentation properties of CD1d, how CD1d controls the function of natural T (iNKT) cells and how CD1d and iNKT cells interact to jump‐start the immune system. It is postulated that the CD1d‐iNKT cell system functions as a sensor, sensing alterations in cellular lipid content by virtue of its affinity for such ligands. The presentation of a neo‐self glycolipid, presumably by infectious assault of antigen‐presenting cells, activates iNKT cells, which promptly release pro‐inflammatory and anti‐inflammatory cytokines and jump‐start the immune system.
Host's innate immune response to fungal and bacterial agents in vitro: up‐regulation of interleukin‐15 gene expression resulting in enhanced natural killer cell activity
Authors: Tran Phay , Ahmad Rasheed , Xu Jingwu , Ahmad Ali , Menezes José 
Published: May 2003

SummaryNatural killer (NK) cells play an important role in the first line of defence against viral infections. We have shown earlier that exposure of human peripheral blood mononuclear cells (PBMC) to viruses results in rapid up‐regulation of NK cell activity via interleukin‐15 (IL‐15) induction, and that this mechanism curtails viral infection in vitro. By using Candida albicans, Escherichia coli and Staphylococcus aureus, we now show here that exposure of PBMC to fungi and bacteria also results in an immediate increase of NK cytotoxicity. Reverse transcriptase–polymerase chain reaction and Western blot analyses as well as the use of antibodies against different cytokines revealed that IL‐15 induction played a predominant role in this NK activation. These results indicate that IL‐15 is also involved in the innate immune response against fungal and bacterial agents.