Abstract:
:The influence of Th2 cytokines in tuberculosis has been a matter of dispute. Here we report that IL-4 has a profound regulatory effect on the infection of BALB/c mice with Mycobacterium tuberculosis. Depletion of IL-4 with a neutralizing mAb caused only evanescent reduction of lung infection, but when combined with i.n. inoculations of IgA anti-mycobacterial alpha-crystallin mAb and mouse rIFN-gamma, we observed a 40-fold reduction of the bacterial counts in the lungs at 3 wks following i.n. infection (p<0.001). In genetically deficient IL-4-/- BALB/c mice, infection in both lung and spleen was substantially reduced for up to 8 wks without further treatment. Reconstitution of IL-4-/- mice with rIL-4 increased bacterial counts to wild-type levels and made the mice refractory to protection by IgA/IFN-gamma. Analysis of the lungs showed increased granulomatous infiltration and proinflammatory mediators in anti-IL-4/IgA/IFN-gamma-treated and infected mice. We conclude that the action of IL-4 in tuberculosis is targeted at macrophages and that it may include an antagonistic effect on their IgA/IFN-gamma-induced activation and nitric oxide production. The described novel immunotherapy, combining treatments with anti-IL-4, IgA antibody and IFN-gamma, has potential for translation toward the passive immunoprophylaxis of tuberculosis.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Buccheri S,Reljic R,Caccamo N,Ivanyi J,Singh M,Salerno A,Dieli Fdoi
10.1002/eji.200636764subject
Has Abstractpub_date
2007-03-01 00:00:00pages
729-37issue
3eissn
0014-2980issn
1521-4141journal_volume
37pub_type
杂志文章abstract::Prior to acquiring a memory phenotype, antigen-activated CD8(+) T cells need to expand and then undergo a contraction phase. Utilizing two different antigenic stimuli, we provide evidence that the tumor necrosis factor receptors OX40 and CD30 integrate synergistic signals during the expansion phase to help maintain CD...
journal_title:European journal of immunology
pub_type: 杂志文章
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abstract::Analysis of proliferation and cytokine production at the single-cell level indicated that proliferation of pre-existing type 2 cytokine(+) human peripheral naive T cells (CD4(+) and CD8(+)) accounts for the accumulation of type 2 T cells in lymphocytes cultured with IL-2, with or without IL-4, and independently from T...
journal_title:European journal of immunology
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830140110
更新日期:1984-01-01 00:00:00
abstract::Antibodies to framework determinants of the VH and V lambda fragments of MOPC 315 and antisera to the VH idiotype determinants of the A 5 A antibody were used to analyze the antigen receptors of mouse T (and B) cells. This was done by using the antibodies as inhibitors in (a) an assay in which the binding of radiolabe...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830100207
更新日期:1980-02-01 00:00:00
abstract::The biochemical behavior and peptide binding properties of a soluble form of the human class II DR4Dw4 molecule (PI-DR4Dw4) were compared to DR4Dw4 molecules containing the transmembrane and cytoplasmic domains that were purified both from B and transfected chinese hamster ovary cells. Recombinant and B cell-derived D...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830230112
更新日期:1993-01-01 00:00:00
abstract::The pro-inflammatory cytokines tumor necrosis factor (TNF) and interleukin-1 (IL-1) have been shown to be primary mediators in the pathogenesis of chronic inflammatory joint diseases. However, the relative contributions of these molecules to the development and progression of disease is not known. In the present study...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830250647
更新日期:1995-06-01 00:00:00
abstract::The immunocytochemical characteristics of large granular lymphocytes (LGL), isolated from the liver sinusoids of euthymic and athymic (nude) rats, were investigated in electron microscopy by the immunoperoxidase technique. The LGL were found positive for MRC OX-8 (natural killer cells and cytotoxic/suppressor T cells)...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830171006
更新日期:1987-10-01 00:00:00
abstract::F protein is found predominantly in the liver and is of unknown function. The protein has been of interest to immunologists in the areas of self tolerance and the immunogenetics of the anti-F protein response. In the mouse there are two alleles (F1 and F2), and although mice are completely tolerant to the self form of...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830210521
更新日期:1991-05-01 00:00:00
abstract::Mismatch repair contributes to hypermutation in B lymphocytes, both by increasing the frequency of mutations and by changing the mutational patterns. In this paper, we investigated whether or not mismatch repair influences activation-induced cytidine deaminase (AID)-mediated hypermutation in a non-B lymphocyte line. W...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200526221
更新日期:2005-07-01 00:00:00
abstract::The cytotoxic response of cell sorter-purified small Lyt-2+ splenic cytotoxic lymphocyte precursors from 10 individual C57BL/6 mice to mutant class I H-2Kbm1 or H-2Dbm14 allodeterminants was analyzed under limiting dilution conditions. The cytotoxic activity of anti-bm1-specific or anti-bm14-specific cytotoxic T lymph...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830161220
更新日期:1986-12-01 00:00:00
abstract::It is widely believed that DC, but not macrophages, prime naïve T cells in vivo. Here, we investigated the ability of CD68-expressing cells (commonly defined as macrophages) in priming autoreactive T cells and initiating collagen-induced arthritis (CIA) in the mouse. For this purpose, a transgenic mouse was developed ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201040598
更新日期:2011-02-01 00:00:00
abstract::Fever is associated with improved survival during infection in endothermic and ectothermic species although the protective mechanisms are largely undefined. Previous studies indicate that fever-range thermal stress increases the binding activity of the L-selectin homing receptor in human or mouse leukocytes, thereby p...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200636421
更新日期:2007-10-01 00:00:00
abstract::Graft-versus-host disease (GVHD) caused by donor T cells attacking recipient tissues is a major cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (alloSCT). Studies have shown that effector memory T (T(EM) ) cells do not cause GVHD but are capable of immune functions post-tr...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201141678
更新日期:2011-09-01 00:00:00
abstract::Development of Th1 and Th2 effector lymphocytes is driven primarily by IL-12 or IL-4, but is also influenced by the strength of antigenic stimulation. However, the mechanism by which TCR signaling contributes to T cell polarization remains elusive. We show that in the presence of IL-12 a short TCR stimulation can lead...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/(SICI)1521-4141(199912)29:12<4092::AID-IMM
更新日期:1999-12-01 00:00:00
abstract::Single-positive thymocytes are the immediate precursors of peripheral recent thymic emigrants (RTE) which develop into mature peripheral T cells. The functional ability of RTE is unclear but their state of differentiation may be relevant to the development of tolerance to peripheral "self" antigens. Since RTE are diff...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830240738
更新日期:1994-07-01 00:00:00
abstract::T-cell homeostasis preserves the numbers, the diversity and functional competence of different T-cell subsets that are required for adaptive immunity. Naïve CD4(+) T (TN ) cells are maintained in the periphery via the common γ-chain family cytokine IL-7 and weak antigenic signals. However, it is not clear how memory C...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201444701
更新日期:2014-10-01 00:00:00
abstract::The CD11c(+) cell population in the non-parenchymal cell population of the mouse liver contains dendritic cells (DC), NK cells, B cells and T cells. In the hepatic CD11c(+) DC population from immunocompetent or immunodeficient [recombinase-activating gene-1 (RAG1)(-/-)] C57BL/6 mice (rigorously depleted of T cells, B ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200324336
更新日期:2004-02-01 00:00:00
abstract::Interactions between CD8+ T cells and endothelial cells are important in both protective and pathologic immune responses. Endothelial cells regulate the recruitment of CD8+ T cells into tissues, and the activation of CD8+ T cells by antigen presentation and costimulatory signals. PD-L1 and PD-L2 are recently described...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200324270
更新日期:2003-11-01 00:00:00
abstract::The inflammatory process that underlies allergic diseases such as asthma is characterized by tissue infiltration of eosinophils and T cells. We have used the Stamper-Woodruff frozen-section assay to characterize the receptors involved in adhesion of human peripheral blood T cells to nasal polyp endothelium (NPE) as a ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/(SICI)1521-4141(199904)29:04<1324::AID-IMM
更新日期:1999-04-01 00:00:00
abstract::Lymphocyte proliferation in response to monocytes pulsed with an antigenic extract of Candida albicans was measured in vitro and the effects of modifying major histocompatibility complex (MHC) class II antigen expression at the surface of the antigen-presenting cells was investigated. The study shows that no simple co...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830160410
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abstract::The transcription factor c-Maf is critical for IL-4 production and the development of Th2 cells, which promote humoral immunity and protect against extracellular parasites. Yet, little else is known of c-Maf function in CD4 cells. Here, we identify a novel role for c-Maf in regulating susceptibility to apoptosis. Over...
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abstract::Reactive oxygen species (ROS) are implicated in the modulation of diverse processes including immune responses. To evaluate the effects of metabolic ROS produced by mitochondria on B-cell function and development, we created transgenic (Tg) mice expressing a phosphorylation-defective mutant of succinate dehydrogenase ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201646342
更新日期:2017-02-01 00:00:00
abstract::Anti-peroxidase antibody (Ab)-secreting hybrids have been produced by fusion of peroxidase (PO)-immunized mouse lymph node cells and immunoglobulin (Ig)-secreting P3-X63-Ag8 (X63) myeloma cells. Identification of Ab-secreting hybrids can be performed as early as day 5 after cell fusion by the hemolytic plaque assay. I...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830090102
更新日期:1979-01-01 00:00:00
abstract::In the fetus the peripheral T cell pool expands as the fetus grows, but the mechanisms that regulate T cell homeostasis during fetal life are unknown. Here, we show that the peripheral T cell pool in the sheep fetus is established by the export from the fetal thymus of twice as many CD8+ as CD4+ thymic emigrants every...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200636096
更新日期:2006-10-01 00:00:00
abstract::Current concepts of activation of the alternative pathway of complement (APC) focus on the central role of an amplification mechanism triggered by C3b which is covalently bound to the surfact of activating substances. Using sulfated polyanions as model substances, an efficient fluid-phase activation of complement is d...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830110405
更新日期:1981-04-01 00:00:00
abstract::Regulatory T (Treg) cells are a constitutively immunosuppressive subtype of T cells that contribute to the maintenance of immunological self-tolerance and immune homeostasis. However, the molecular mechanisms involved in the regulation of Treg cells remain unclear. In the present study, we identified ubiquitously expr...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201343394
更新日期:2014-02-01 00:00:00
abstract::The TNF member LIGHT also known as TL4 or TNFSF14) can play a major role in cancer control via its two receptors; it induces tumor cell death through lymphotoxin-beta receptor (LT-betaR) and ligation to the herpes virus entry mediator (HVEM) amplifies the immune response. By studying the effect of LIGHT in the transcr...
journal_title:European journal of immunology
pub_type: 杂志文章
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更新日期:2009-09-01 00:00:00
abstract::As we approach the centenary of Elie Metchnikoff's Nobel Prize (1908), it is opportune to reflect upon the history of macrophage immunobiology, take stock of current knowledge and anticipate questions for the future. Starting from his appreciation of phagocytosis as an important determinant of host defence against inf...
journal_title:European journal of immunology
pub_type: 历史文章,杂志文章,评审
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更新日期:2007-11-01 00:00:00
abstract::Fourteen noncytotoxic human helper T cell clones were examined for autocrine proliferative responses and cytotoxicity to tumor cells after stimulation with 12-O-tetradecanoylphorbol 13-acetate (TPA) and ionomycin (Io). Although all clones responded to alloantigen, they could be divided into two groups based on their p...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830180729
更新日期:1988-07-01 00:00:00
abstract::Cold agglutinins (CA) are autoantibodies that bind to erythrocyte carbohydrates at low temperatures and induce complement-mediated cell lysis, thus causing hemolytic anemia. Tolerance mechanisms towards CA-expressing B cells and the factors inducing pathogenic CA production are unknown. In order to develop an animal m...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/1521-4141(2000)30:8<2290::AID-IMMU2290>3.0
更新日期:2000-08-01 00:00:00