Search results for " Immune system"
showing 10 items of 893 documents
Activation of the human immune system via toll-like receptors by the oncolytic parvovirus H-1.
2012
This study aimed to investigate the function of toll-like receptors (TLRs) during oncolytic parvovirus H-1 (H-1PV)-induced human immune responses. First, the role of TLRs in the activation of the NFκB transcription factor was characterized; second, the immunologic effects of H-1PV-induced tumor cell lysates (TCL) on human antitumor immune responses were evaluated. A human ex vivo model was used to study immune responses with dendritic cells (DCs). Human embryonic kidney cells (HEK293) transfected to stably express TLRs were used as potential human DC equivalents to further investigate the role of specific TLRs during immune activation. TLR3 and TLR9 were activated by H-1PV infection, which …
Impaired Mast Cell-Driven Immune Responses in Mice Lacking the Transcription Factor NFATc2
2009
Abstract The three calcium-dependent factors NFATc1, c2, and c3 are expressed in cells of the immune system and play pivotal roles in modulating cellular activation. With regard to NFATc2, it was reported that NFATc2-deficient mice display increased immune responses in several models for infection and allergy in vivo. This led to the assumption that NFATc2 is involved in the maintenance of immune homeostasis. Using the synthetic TLR7 agonist imiquimod as an adjuvant in epicutaneous peptide immunization, we observed that both the inflammatory reaction and the peptide-specific CTL response are severely impaired in NFATc2-deficient mice. Detailed analyses revealed that early production of proi…
Alloreactive and H-2-restricted Lyt 23 cytotoxic T lymphocytes derive from a common pool of antecedent Lyt 123 precursors.
1980
If the collaborative requirement of Lyt 1 T helper cells is bypassed by the Lyt 1 T cell-derived mediator of T help, termed Il-2, upon antigenic stimulation, PNA+ Lyt 123 thymocytes differentiate into either alloreactive or H-2-restricted PNA- Lyt 23 cytotoxic effector cells. Along the differentiation pathway from Lyt 123 leads to 23 effector cells, cytolytic activity is carried out by T cells that still express the Lyt 123 phenotype. The data establish that Lyt 23 CTL are produced by differentiation from antecedent Lyt 123 cells.
Precursor frequency can compensate for lower TCR expression in T cell competition during priming in vivo.
2006
The factors controlling clonal dominance of cytotoxic T lymphocyte (CTL) responses are currently not well understood. To study the functional impact of the strength of the interaction of a T cell with an antigen-presenting cell in this context, we established a new mouse model comprised of two T cell receptor (TCR)-transgenic strains expressing the identical TCR in differing amounts, hence providing two CTL clones with different avidities but identical specificity and affinity. Utilizing this new model, we show that upon antigen challenge higher-avidity CTL expand at the expense of moderate-avidity CTL in vivo if present in equal numbers. Beyond this, moderate-avidity T cells can also contr…
The T Cell Receptor (TCR) in HLA-B27-Restricted T Cell Responses - an Introduction
1996
Recent data indicate that cytotoxic T lymphocytes (CTL) are involved in the pathogenesis of HLA-B27-associated spondylarthropathies. In the absence of clearly defined "arthritogenic" bacterial or self peptides that are presented by HLA-B27 and recognized by such CD8+CTL, one approach has been to investigate the T cell repertoire of lesional cellular infiltrates by determining T cell receptor (TCR) variable (V) gene segment frequencies. Furthermore, the TCR V alpha and V beta chains of HLA-B27-restricted CTL clones, notably the putative peptide-contacting CDR3-regions of these TCRs, have been sequenced. This article will give a short review of the current literature on the topology of the TC…
Fine specificity and cytolytic activity of continuously growing alloreactive cytotoxic T lymphocyte clones.
1980
The role of Lyt 1+ T-cell-derived secondard CTL inducing factor allowed the cloning of alloreactive cytotoxic T lymphocytes (CTL) by the limiting dilution approach. Several monoclonal cell lines were established in vitro. The lytic activity of some of the cell lines exceeded that of CTL from bulk cultures; that is, 50% of the target cells were lysed at an effector to target cell ratio of 0.04:1. The fine specificity of individual CTL clones is discussed.
Herpes-Simplex-virus-specific, H-2Dk-restricted T lymphocytes bear receptors for H-2Dd alloantigen.
1980
Cytotoxic T lymphocytes generated in the course of an HSV-infection of CBA (H-2k) mice not only lyse syngeneic, virus-infected target cells but also cross-react with noninfected taraget cells expressing the Dd alloantigen. On the effector cell level, this alloreactivity is mediated by virus-specific CTL's that are restricted to H-2Dk determinants. On the prekiller cell level, the anti-HSV-reactive T cells exhibiting cross-reactivity for Dd alloantigen could be positively selected on H-2d spleen-cell monolayers. After differentiation into cytolytic effector cells, target cells expressing Dd alloantigens and syngeneic HSV-infected target were lysed with equal efficiency. The results imply tha…
RNA Transfer by Electroporation into Mature Dendritic Cells Leading to Reactivation of Effector-Memory Cytotoxic T Lymphocytes: A Quantitative Analys…
2005
Previous studies have analyzed transfer of RNA-encoded tumor-associated antigens (TAAs) into immature dendritic cells (DCs) because of their exceptional ability to internalize antigens. Concerns have been raised regarding the use of immature DCs in clinical studies because of their capacity to tolerize T cells. Therefore, we focused on optimizing RNA transfer into mature DCs using the method of electroporation and obtained high protein expression in 90% of mature DCs. Particular emphasis was placed on quantifying RNA transfer. Reconstitution of peptide-MHC (pMHC) ligands on RNA-pulsed DCs was measured with the help of effector-memory cytotoxic T lymphocytes (CTLs) specific for the melanoma-…
T-cell-derived helper factor allows Lyt 123 thymocytes to differentiate into cytotoxic T lymphocytes.
1979
IT is generally accepted that the diversity of T-cell responsiveness is generated in the thymus1. It is also known that except for a few Lyt 1 cells all thymocytes express the Lyt 123 phenotype2,3. Surprisingly, thymocytes are poorly responsive in vitro4, and only the medullary thymocytes, comprising 5–10% of the total thymic cell population, show an in vitro responsiveness comparable with that of peripheral T cells5. Cortical thymocytes, comprising 90–95% of all thymocytes, have previously been considered to be immature and immunologically incompetent4. The result reported here show that thymocytes are able to generate alloantigen-, virus- and hapten-specific cytotoxic T lymphocytes (CTL),…
NLRP3 controls ATM activation in response to DNA damage
2020
The DNA damage response (DDR) is essential to preserve genomic integrity and acts as a barrier to cancer. The ATM pathway orchestrates the cellular response to DNA double strand breaks (DSBs), and its attenuation is frequent during tumorigenesis. Here, we show that NLRP3, a Pattern Recognition Receptor known for its role in the inflammasome complex formation, interacts with the ATM kinase to control the early phase of DDR, independently of its inflammasome activity. NLRP3 down-regulation in human bronchial epithelial cells impairs ATM pathway activation as shown by an altered ATM substrate phosphorylation profile, and due to impaired p53 activation, confers resistance to acute genomic stres…