Search results for "Interleukin 21"
showing 10 items of 178 documents
Transforming growth factor induced FoxP3+ regulatory T cells suppress Th1 mediated experimental colitis
2006
Background and aims: The imbalance between effector and regulatory T cells plays a central role in the pathogenesis of inflammatory bowel diseases. In addition to the thymus, CD4+CD25+ regulatory T cells can be induced in the periphery from a population of CD25− T cells by treatment with transforming growth factor β (TGF-β). Here, we analysed the in vivo function of TGF-β induced regulatory T (Ti-Treg) cells in experimental colitis. Methods: Ti-Treg cells were generated in cell culture in the presence or absence of TGF-β and tested for their regulatory potential in experimental colitis using the CD4+CD62L+ T cell transfer model. Results: Ti-Treg cells significantly suppressed Th1 mediated c…
Induction of tumor peptide-specific cytotoxic T cells under serum-free conditions by mature human dendritic cells
2000
Tumor vaccination strategies using antigen-pulsed dendritic cells (DC) are currently under development. We established an in vitro system using cultured DC from HLA-typed volunteers for the induction of tumor peptide-specific CD8+ T cells. The strength and specificity of the resulting CTL responses were investigated. For stimulation of syngeneic CD8+ T cells two well-defined DC populations were generated: CD1a+ immature DC cultured in the presence of GM-CSF and IL-4 and mature CD83+ DC generated by additional stimulation with a cytokine cocktail. Stimulations were performed under serum-free conditions and in the absence of exogenous cytokines. Analysis of T cell responses showed that mature…
Identification of HLA-A*0201-Restricted T Cell Epitopes Derived from the Novel Overexpressed Tumor Antigen Calcium-Activated Chloride Channel 2
2002
Abstract Vaccination against tumor Ags may become a promising treatment modality especially in cancer types where other therapeutic approaches fail. However, diversity of tumors requires that a multitude of Ags become available. Differential expression in normal vs cancerous tissues, both at the mRNA and the protein level, may identify Ag candidates. We have previously compared transcripts from squamous cell lung cancer and normal lung tissue using differential display analysis, and found a transcript that was overexpressed in malignant cells and was identical with the calcium-activated chloride channel 2 (CLCA2) gene. We have now selected HLA-A2-restricted peptides from CLCA2, and have gen…
CD4 blockade directly inhibits mouse and human CD4+ T cell functions independent of Foxp3+ Tregs
2013
CD4(+) helper T cells orchestrate protective immunity against pathogens, yet can also induce undesired pathologies including allergies, transplant rejection and autoimmunity. Non-depleting CD4-specific antibodies such as clone YTS177.9 were found to promote long-lasting T cell tolerance in animal models. Thus, CD4 blockade could represent a promising therapeutic approach for human autoimmune diseases. However, the mechanisms underlying anti-CD4-induced tolerance are incompletely resolved. Particularly, multiple immune cells express CD4 including Foxp3(+) regulatory T cells (Tregs) and dendritic cells (DCs), both controlling the activation of CD4(+)Foxp3(-) helper T cells. Utilizing mixed le…
T cell avidity determines the level of CTL activation
2004
To investigate the influence of avidity on T cell activation in vitro and in vivo, we analyzed T cells from St40 and St42 mice, which express the same transgenic TCR specific for an E1a-derived epitope of adenovirus type 5 with different expression levels and therefore different avidities. Splenocytes from both strains showed comparable cytolytic activities and required identical peptide concentrations for efficient target cell lysis and up-regulation of activation markers. However, the kinetics of CD25 up-regulation were strikingly different: whereas the majority of the high-avidity St42 T cells up-regulated the IL-2Ralpha chain within a few hours, low-avidity St40 T cells expressed only 5…
Definition of the HLA-A2 restricted peptides recognized by human CD8+ effector T cells by flow-assisted sorting of the CD8+ CD45RA+ CD28– T cell subp…
2003
SUMMARY In response to antigenic stimulation, naive MHC-class I restricted and antigen-specific CD8+ CD45RA+ CD28+ T cells undergo clonal expansion, differentiate into CD8+ CD45RO+ memory T cells and convert to CD8+ CD45RA+ CD28− T cells displaying potent immune effector functions upon re-encounter with the nominal antigen. We show that the effector CD8+ CD45RA+ CD28– T cell subset is expanded in peripheral blood lymphocytes (PBL) from patients with human papilloma virus (HPV)+ cervical lesions as well as in PBL from patients with pulmonary tuberculosis. Flow-cytometric cell sorted CD8+ CD45RA+ CD28– and CD8+ CD45RA+ CD28– T cells were tested for recognition of HLA-A2 restricted peptides de…
T helper cell polarisation in coeliac disease: any (T-)bet ?
2004
Recent data strongly support the view that coeliac disease is a Th1 mediated inflammatory disease as both interferon γ production and T-bet levels in gut infiltrating cells are upregulated The puzzling observation on high interferon γ (IFN-γ) but low interleukin (IL)-12 levels in coeliac disease (CD) has resulted in questions about the underlying principles of T helper cell polarisation. In this issue of G ut ,1 the molecular basis of T helper cell polarisation in CD has been illuminated by the finding that T-bet, the master transcription factor of T helper cell type 1 (Th1) cells, is upregulated in this disease [see page 1090] . The past decade has witnessed a dramatic improvement in our p…
Human intestinal Vdelta1+ lymphocytes recognize tumor cells of epithelial origin.
1996
gammadelta T cells can be grouped into discrete subsets based upon their expression of T cell receptor (TCR) variable (V) region families, their tissue distribution, and their specificity. Vdelta2+ T cells constitute the majority of gammadelta T cells in peripheral blood whereas Vdelta1+T cells reside preferentially in skin epithelium and in the intestine. gammadelta T cells are envisioned as first line host defense mechanisms capable of providing a source of immune effector T cells and immunomodulating cytokines such as interleukin (IL) 4 or interferon (IFN) gamma. We describe here the fine specificity of three distinct gammadelta+ tumor-infiltrating lymphocytes (TIL) obtained from patient…
Interleukin 1 stimulates T lymphocytes to produce granulocyte-monocyte colony-stimulating factor.
1988
T lymphocytes are thought to cooperatively interact with monocytes to produce colony-stimulating factors (CSF). However, little is known about monocyte-mediated signals leading to CSF-secretion by T lymphocytes, although soluble monocyte products have been implicated. We have employed monoclonal antibody anti-T3B covalently coupled to CnBr-activated Sepharose 4B beads, to show that multimeric ligation of T cell antigen receptor leads to T cell receptiveness to interleukin 1 (IL-1), as indicated by T cell production of CSF, which induces growth of myeloid progenitor cells into neutrophil, eosinophil, and monocyte colonies. To investigate the molecular basis of these findings, total RNA was e…
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…