Search results for "ZAP70"
showing 10 items of 41 documents
In vitro generated human memory-like T cells are CD95 type II cells and resistant towards CD95-mediated apoptosis
2006
An adaptive immune response implies expansion of activated T cells and subsequent elimination to maintain homeostasis in a process called activation-induced cell death. Some cells, however, differentiate into memory cells and ensure a strong secondary immune response. To analyze the apoptosis phenotype of memory T cells on a cellular and molecular level, we have established an in vitro model of T cell activation and generation of cells phenotypically and functionally similar to memory cells. These long-term cultured T cells show a CD95-resistant phenotype, although they are still sensitive towards TCR/CD3-mediated apoptosis. Biochemical analysis revealed that these cells shift from CD95 typ…
From interleukin-9 to T helper 9 cells
2012
Abstract Interleukin-9 (IL-9), cloned more than 20 years ago, was initially thought to be a Th2-specific cytokine. This assumption was initially confirmed by functional analyses showing that both IL-9 and Th2 cells play an important role in the pathogenesis of asthma, IgE class switch recombination, and resolution of parasitic infections. However, recently it was shown that IL-9-producing CD4(+) T cells represent the discrete T helper subset Th9 cells. Herein, we will review the cytokines and transcription factors known to promote the development of Th9 cells and their potential functional properties in relation to the biological activities of IL-9. In addition, we will discuss how Th9 cell…
Drug-induced expansion and differentiation of Vγ9Vδ2 T cells in vivo: The role of exogenous IL-2
2005
Human Vgamma9Vdelta2 T cells recognize nonpeptidic Ags generated by the 1-deoxy-d-xylulose 5-phosphate (many eubacteria, algae, plants, and Apicomplexa) and mevalonate (eukaryotes, archaebacteria, and certain eubacteria) pathways of isoprenoid synthesis. The potent Vgamma9Vdelta2 T cell reactivity 1) against certain cancer cells or 2) induced by infectious agents indicates that therapeutic augmentations of Vgamma9Vdelta2 T cell activities may be clinically beneficial. The functional characteristics of Vgamma9Vdelta2 T cells from Macaca fascicularis (cynomolgus monkey) are very similar to those from Homo sapiens. We have found that the i.v. administration of nitrogen-containing bisphosphonat…
Cyclic adenosine monophosphate is a key component of regulatory T cell–mediated suppression
2007
Naturally occurring regulatory T cells (T reg cells) are a thymus-derived subset of T cells, which are crucial for the maintenance of peripheral tolerance by controlling potentially autoreactive T cells. However, the underlying molecular mechanisms of this strictly cell contact–dependent process are still elusive. Here we show that naturally occurring T reg cells harbor high levels of cyclic adenosine monophosphate (cAMP). This second messenger is known to be a potent inhibitor of proliferation and interleukin 2 synthesis in T cells. Upon coactivation with naturally occurring T reg cells the cAMP content of responder T cells is also strongly increased. Furthermore, we demonstrate that natur…
Strong and sustained effector function of memory- versus naïve-derived T cells upon T-cell receptor RNA transfer: Implications for cellular therapy
2012
Current protocols used to select CMV-specific T cells for adoptive immunotherapy focus on virus-specific memory T cells from seropositive donors. However, this strategy is not feasible in patients undergoing allogeneic haematopoietic stem-cell transplantation (HSCT) from CMV-seronegative donors. Here, we redirected T cells of CMV-seronegative donors with a human genetically engineered TCR recognizing an HLA-A*0201-binding peptide epitope of CMVpp65. To facilitate clinical translation of this approach, we used a non-viral expression system based on in vitro transcribed RNA and electroporation. Although memory and naive-derived T-cell subsets were both efficiently transfected by TCR-RNA, memo…
Induction of regulatory Tr1 cells and inhibition of TH17 cells by IL-27
2011
Accumulating evidence indicates that IL-27, a member of the IL-12 family of cytokines, alleviates the severity of autoimmune diseases in both mice and men. The IL-27-induced activation of signal transducer and activator of transcription (Stat)1 and Stat3 promotes the generation of IL-10- producing type 1 regulatory T (Tr1) cells that inhibit effector T cells. In addition, IL-27 also suppresses the development of pathogenic IL-17-producing CD4(+) T cells (T(H)17) cells suggesting that pharmacological manipulations of IL-27 signaling pathway could be exploited therapeutically in regulating tissue inflammation. Here, we review how IL-27 controls inflammation through the regulation of Tr1 and T…
B-Raf-mediated signaling pathway regulates T cell development
2008
The activities of the Raf kinase family proteins control extracellular signal-regulated kinase (ERK) activation in many aspects of cellular responses. However, the relative contributions of individual isozymes to cellular functions including T cell responses are still unclear. In addition to Raf-1, another Raf family kinase, B-Raf, is expressed in murine thymocytes and peripheral T cells, and its activation was induced by TCR stimulation. Here, we investigated the function of B-Raf in development of T cells by generating chimeric mice in which a T cell-compromised host was reconstituted with fetal liver-derived cells from embryonic lethal B-Raf-deficient mice. Although B-Raf was dispensable…
Serum metabolome analysis by 1H-NMR reveals differences between chronic lymphocytic leukaemia molecular subgroups.
2010
Chronic lymphocytic leukaemia (CLL) is a heterogeneous disease exhibiting variable clinical course and survival rates. Mutational status of the immunoglobulin heavy chain variable regions (IGHVs) of CLL cells offers useful prognostic information for high-risk patients, but time and economical costs originally prevented it from being routinely used in a clinical setting. Instead, alternative markers of IGHV status, such as zeta-associated protein (ZAP70) or messenger RNA levels are often used. We report a (1)H-NMR-based metabolomics approach to examine serum metabolic profiles of early stage, untreated CLL patients (Binet stage A) classified on the basis of IGHV mutational status or ZAP70. M…
The NK Cell Response to Mouse Cytomegalovirus Infection Affects the Level and Kinetics of the Early CD8+ T-Cell Response
2012
ABSTRACT Natural killer (NK) cells and CD8 + T cells play a prominent role in the clearance of mouse cytomegalovirus (MCMV) infection. The role of NK cells in modulating the CD8 + T-cell response to MCMV infection is still the subject of intensive research. For analyzing the impact of NK cells on mounting of a CD8 + T-cell response and the contribution of these cells to virus control during the first days postinfection (p.i.), we used C57BL/6 mice in which NK cells are specifically activated through the Ly49H receptor engaged by the MCMV-encoded ligand m157. Our results indicate that the requirement for CD8 + T cells in early MCMV control inversely correlates with the engagement of Ly49H. W…
β2Integrin deficiency yields unconventional double-negative T cells distinct from mature classical natural killer T cells in mice
2009
Expressed on leucocytes, beta(2) integrins (CD11/CD18) are specifically involved in leucocyte function. Using a CD18-deficient (CD18(-/-)) mouse model, we here report on their physiological role in lymphocyte differentiation and trafficking. CD18(-/-) mice present with a defect in the distribution of lymphocytes with highly reduced numbers of naïve B and T lymphocytes in inguinal and axillary lymph nodes. In contrast, cervical lymph nodes were fourfold enlarged harbouring unconventional T-cell receptor-alphabeta (TCR-alphabeta) and TCR-gammadelta CD3(+) CD4(-) CD8(-) (double-negative; DN) T cells that expanded in situ. Using adoptive transfer experiments, we found that these cells did not h…