Search results for "Antibodies."
showing 10 items of 1857 documents
Activated glycoprotein A repetitions predominant (GARP)-expressing regulatory T cells inhibit allergen-induced intestinal inflammation in humanized m…
2015
Background Recently, we developed a humanized mouse model of allergen-induced IgE-dependent gut inflammation in PBMC-engrafted immunodeficient mice. Objective In the present study, we wanted to investigate the role of regulatory T (Treg) cells and their activation status in this model. Methods Nonobese diabetic-severe combined immunodeficiency-γc −/− mice were injected intraperitoneally with human PBMCs from allergic donors together with the respective allergen or NaCl as control in the presence or absence of different concentrations of CD4 + CD25 + Treg cells of the same donor. After an additional allergen boost 1 week later, mice were challenged with the allergen rectally on day 21 and gu…
Impaired immune response to Candida albicans in aged mice
2006
The prevalence of opportunistic fungal infections has increased dramatically among the aged population in recent years. This work investigated the effect of ageing on murine defences against Candida albicans. Aged C57BL/6 mice that were experimentally infected intravenously had a significantly impaired survival and a higher tissue fungal burden compared with young mice. In vitro production of tumour necrosis factor (TNF)-α by macrophages from aged mice in response to yeast cells and hyphae of C. albicans was significantly lower than production by macrophages from young mice. In vitro production of cytokines, such as TNF-α and gamma interferon (IFN-γ), by antigen-stimulated splenocytes from …
Induction of CD4+/CD25+ regulatory T cells by targeting of antigens to immature dendritic cells
2003
AbstractCoupling of ovalbumin (OVA) to anti–DEC-205 monoclonal antibody (mAb) (αDEC) induced the proliferation of OVA-specific T cells in vivo. Expansion was short-lived, caused by dendritic cells (DCs), and rendered T cells anergic thereafter. Phenotypic analysis revealed the induction of CD25+/CTLA-4+ T cells suppressing proliferation and interleukin-2 (IL-2) production of effector CD4+ T cells. The findings were supported by 2 disease models: (1) CD4+ T-cell–mediated hypersensitivity reactions were suppressed by the injection of αDEC-OVA and (2) the application of hapten-coupled αDEC-205 reduced CD8+ T-cell–mediated allergic reactions. Thus, targeting of antigens to immature DCs through …
A new model of chronic colitis in SCID mice induced by adoptive transfer of CD62L+ CD4+ T cells: insights into the regulatory role of interleukin-6 o…
2003
<i>Objective:</i> The proinflammatory cytokine interleukin (IL)-6 is involved in various chronic inflammatory processes. IL-6 is a predominant cytokine produced by lamina propria T cells in Crohn’s disease and experimental colitis. This study was designed to examine the effect of a neutralizing IL-6-receptor (IL-6R) antibody on the programmed cell death of mucosal T cells in the CD62L+ CD4+ SCID transfer model of chronic experimental colitis in mice and to gain more insight into the pathogenesis of this transfer colitis model. <i>Methods:</i> For adoptive transfer, we isolated CD62L+ CD4+ double-positive T cells from wild-type BALB/c mice followed by intraperitoneal …
Local blockade of IL-6R signaling induces lung CD4+ T cell apoptosis in a murine model of asthma via regulatory T cells.
2007
We previously reported high levels of the soluble form of the IL-6R (sIL-6R) in the airways of asthmatic subjects. Here, we analyzed the IL-6R effects on Th2 cell survival in the lung by locally antagonizing sIL-6R-mediated trans-signaling with a designer fusion protein (gp130-Fc) as well as IL-6R signaling with an antibody against the gp80 unit of the IL-6R (alphaIL-6R) in a murine model of asthma after ovalbumin peptide (OVA) sensitization and challenge. Blockade of the sIL-6R led to a significant decrease in inflammatory cells by an apoptosis-independent mechanism. In contrast, local treatment with alphaIL-6R antibodies that also block signaling via the membrane-bound IL-6R (mIL-6R) led …
Opening a Niche for Therapy: Local Lymphodepletion Helps the Immune System to Fight Melanoma
2014
In this issue, Fujiwara et al. report that local ablation of CD4+ T cells in a murine B16 melanoma model, together with concomitant activation of the immune system by OX40L, leads to complete rejection of the melanomas. Rejection was driven mainly by CD8+ T cells, which infiltrated the melanomas and secreted sizeable amounts of IFN-γ. However, CD8+ T-cell infiltration also caused the recruitment of immunosuppressive myeloid-derived suppressor cells (MDSCs). Although these cells did not prevent the rejection of the melanomas, in clinical settings the long-term repopulation of tumors by MDSCs may counteract successful treatment. Thus, local ablation of CD4+ leukocytes may improve anti-melanom…
Selection of distinct Valpha/beta T-cell receptor families during in vivo and in vitro T-cell maturation.
1999
The experimental conditions influencing the use of Valphabeta TCR families were examined in lymph node (LN) cells from peptide-immunized C57BL/6 and Vbeta8.2 transgenic mice. Expanded proportions of Vbeta5, Vbeta8.2, Vbeta9, Vbeta12 and Vbeta14 positive cells and an association of Vbeta8.2 with Valpha11 was found in freshly harvested 8-day or 34-day immune LN cells. In contrast, peptide-specific T-cell lines generated in vitro from 8-day immune lymph node cells were found to be almost exclusively of the Valpha2/Vbeta12 family. However, T-cell lines originating from Vbeta8.2 transgenic mice did not show preferential Valpha usage. Anti-Vbeta8.2 antibody produced different effects: when added …
Broad clonal heterogeneity of antigen-specific CD4+ T-cells localizing at the site of disease during tuberculosis
1999
The repertoire of CD4+ T-lymphocytes was investigated in six patients affected by tuberculosis, who had a negative PPD skin test at diagnosis. Polyclonal CD4+ T-cell lines from the peripheral blood failed to proliferate to PPD and to the 16- or 38-kDa proteins of Mycobacterium tuberculosis, while CD4+ T-cell lines from the site of disease responded to PPD, and to the 16- and 38-kDa proteins, and derived epitopes in vitro. The repertoire of CD4+ T-cells accumulating at the site of disease was found to be widely heterogeneous as demonstrated by the finding that at least seven different peptides from the 16- and 38-kDa proteins were recognized by every patient. These results indicate that CD4+…
IL-28A Is a Key Regulator of T-Cell–Mediated Liver Injury via the T-Box Transcription Factor T-Bet
2006
Background & Aims: T-cell–mediated fulminant hepatitis is a potentially life-threatening event for which the underlying pathogenic mechanisms are not fully understood. Here, we demonstrate a key regulatory role of IL-28A in T-cell–mediated hepatitis. Methods: We cloned the murine IL-28A gene by reverse-transcription polymerase chain reaction, assessed the effects of recombinant IL-28A, and generated IL-28A–transgenic mice. Results: IL-28A induced TH1 cytokine production by CD4+ T lymphocytes in a T-bet–dependent manner and was up-regulated in a murine model of T-cell–mediated hepatitis upon Con A administration. In vivo, CD4+ T cells from newly created IL-28A–transgenic animals revealed an …
IL-2 receptor beta-chain signaling controls immunosuppressive CD4+ T cells in the draining lymph nodes and lung during allergic airway inflammation i…
2008
Abstract IL-2 influences both survival and differentiation of CD4+ T effector and regulatory T cells. We studied the effect of i.n. administration of Abs against the α- and the β-chains of the IL-2R in a murine model of allergic asthma. Blockade of the β- but not the α-chain of the IL-2R after allergen challenge led to a significant reduction of airway hyperresponsiveness. Although both treatments led to reduction of lung inflammation, IL-2 signaling, STAT-5 phosphorylation, and Th2-type cytokine production (IL-4 and IL-5) by lung T cells, IL-13 production and CD4+ T cell survival were solely inhibited by the blockade of the IL-2R β-chain. Moreover, local blockade of the common IL-2R/IL-15R…