Search results for "ZAP70"
showing 10 items of 41 documents
T-bet as a possible therapeutic target in autoimmune disease
2002
The prominent role of pro-inflammatory cytokines produced by T helper-1 (T(H1)) cells in regulating autoimmune responses in vitro and in vivo has been demonstrated. Recent observations of T cell polarisation by regulatory transcription factors--especially T-bet (T-box expressed in T cells)--raise the question of their influence in controlling autoimmune diseases. Here, the authors summarise recent observations of the role of T-bet in controlling chronic inflammatory and autoimmune diseases and discuss the implications of these findings for future therapeutic approaches.
T cells in reactive arthritis
1993
T cells appear to play a major role in the development, maintenance and also resolution of reactive arthritis (ReA). Recent advances in understanding the processes involved in T cell activation now allow us to examine the peripheral blood and synovial fluid T cell responses to given "arthritogenic" microorganisms in terms of antigen specificity, epitope identification, cytokine secretion patterns, HLA restriction and the role of different T cell subsets in ReA. Peripheral blood bulk proliferation and limiting dilution studies provide evidence that the peripheral T cell response against arthritis-associated gram-negative bacteria is decreased in patients developing immunological sequelae suc…
The NFκB-inducing kinase is essential for the developmental programming of skin-resident and IL-17-producing γδ T cells
2015
γδ T cells contribute to first line immune defense, particularly through their ability for rapid production of proinflammatory cytokines. The cytokine profile of γδ T cells is hard-wired already during thymic development. Yet, the molecular pathways underlying this phenomenon are incompletely understood. Here we show that signaling via the NFκB-inducing kinase (NIK) is essential for the formation of a fully functional γδ T cell compartment. In the absence of NIK, development of Vγ5+ dendritic epidermal T cells (DETCs) was halted in the embryonic thymus, and impaired NIK function caused a selective loss of IL-17 expression by γδ T cells. Using a novel conditional mutant of NIK, we could show…
Cryptochrome-1 expression: a new prognostic marker in B-cell chronic lymphocytic leukemia
2008
Chronic lymphocytic leukemia is an adult-onset leukemia with a heterogeneous clinical behavior. When chronic lymphocytic leukemia cases were divided on the basis of IgVH mutational status, widely differing clinical courses were revealed. Since IgVH sequencing is difficult to perform in a routine diagnostic laboratory, finding a surrogate for IgVH mutational status seems an important priority. In the present study, we proposed the use of Cryptochrome- 1 as a new prognostic marker in early-stage chronic lymphocytic leukemia. Seventy patients (Binet stage A, without treatment) were included in the study. We correlated Cryptochrome-1 mRNA with well established prognostic markers such as IgVH mu…
B7/CD28 costimulation of T cells induces a distinct proteome pattern.
2005
Effective immune strategies for the eradication of human tumors require a detailed understanding of the interaction of tumor cells with the immune system, which might lead to an optimization of T cell responses. To understand the impact of B7-mediated costimulation on T cell activation comprehensive proteome analysis of B7-primed T cell populations were performed. Using this approach we identified different classes of proteins in T cells whose expression is either elevated or reduced upon B7-1- or B7-2-mediated CD28 costimulation. The altered proteins include regulators of the cell cycle and cell proliferation, signal transducers, components of the antigen processing machinery, transporters…
Cutting Edge: Trans-Signaling via the Soluble IL-6R Abrogates the Induction of FoxP3 in Naive CD4+CD25− T Cells
2007
Abstract Chronic inflammatory diseases may develop when regulatory T cells (Tregs) fail to control the balance between tolerance and immunity. Alternatively, activated immune cells might prevent the induction or activation of Tregs in such diseases. In this study, we demonstrate that trans-signaling into T cells via the soluble IL-6 receptor completely abrogates the de novo induction of adaptive Tregs. Mechanistically, IL-6 trans-signaling augmented the expression of the TGF-β signaling inhibitor SMAD7. Consequently, SMAD7 overexpression in T cells using newly created transgenic mice rendered CD4+CD25− T cells resistant to the induction of FoxP3. Finally, IL-6 trans-signaling inhibited Treg…
The ubiquitin-specific protease USP8 is critical for the development and homeostasis of T cells
2015
The modification of proteins by ubiquitin has a major role in cells of the immune system and is counteracted by various deubiquitinating enzymes (DUBs) with poorly defined functions. Here we identified the ubiquitin-specific protease USP8 as a regulatory component of the T cell antigen receptor (TCR) signalosome that interacted with the adaptor Gads and the regulatory molecule 14-3-3β. Caspase-dependent processing of USP8 occurred after stimulation of the TCR. T cell-specific deletion of USP8 in mice revealed that USP8 was essential for thymocyte maturation and upregulation of the gene encoding the cytokine receptor IL-7Rα mediated by the transcription factor Foxo1. Mice with T cell-specifi…
The mitochondrial protein TCAIM regulates activation of T cells and thereby promotes tolerance induction of allogeneic transplants.
2013
Primary T cell activation and effector cell differentiation is required for rejection of allogeneic grafts in naive recipients. It has become evident, that mitochondria play an important role for T cell activation. Expression of several mitochondrial proteins such as TCAIM (T cell activation inhibitor, mitochondrial) is down-regulated upon T cell receptor triggering. Here we report that TCAIM inhibited spontaneous development of memory and effector T cells. CD4(+) T cells from Tcaim knock-in (KI) mice showed reduced activation, cytokine secretion and proliferation in vitro. Tcaim KI T cells tolerated allogeneic skin grafts upon transfer into Rag-1 KO mice. CD4(+) and CD8(+) T cells from the…
Tonic T cell signalling and T cell tolerance as opposite effects of self-recognition on dendritic cells.
2010
Naive T cells spend most of their time scanning the surface of dendritic cells (DCs), indicating that self-MHC/T cell receptor (TCR) interactions between these immune cells occur routinely in peripheral organs during the steady state. Peripheral self-MHC recognition on DCs drives seemingly opposing effects in the absence of inflammatory stimuli such as deletion of certain self-reactive T cells as well as maintenance of the T cell responsiveness to antigen, both of which shape the T cell repertoire and regulate T cell responses. Here we review recent data on the role of self-MHC recognition on steady-state DCs in the periphery and propose that interactions between T cells and steady-state DC…
With a little help from my old T cell: Memory follicular T helper cells driving autoimmunity?
2014
It has long been known that the B cell repertoire includes cells that are capable of producing autoantibodies and that these cells can be found in humans and also in wild type strains of laboratory mice; however, normally, these B cells do not give rise to plasma cells, and thus do not fulfil their autoimmune potential. In this issue of the European Journal of Immunology, Nusser et al. [Eur. J. Immunol. 2014. 44: 2893–2902] dissect the mechanism by which these B cells are activated and autoantibodies are produced. The authors demonstrate that T cells, most likely antigen-specific, which accumulate with age or as a result of homeostatic proliferation, provide essential help to these autoreac…