Search results for "TOXICITY"

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…

Enhanced susceptibility to cytotoxic T lymphocytes without increase of MHC class I antigen expression after conditional overexpression of heat shock …

1999

Antigenic peptides have been found associated with heat shock proteins (HSP) including cytoplasmic HSP70 and heat shock cognate protein 70 as well as the endoplasmic reticulum-resident glucose-regulated protein 94. Recently, HSP70 transfection has been reported to increase MHC class I cell surface expression and antigen presentation on mouse melanoma B16 cells (Wells et al., Int. Immunol. 1998. 10: 609). To analyze the effect of HSP70 on MHC class I cell surface expression and lysability of target cells we transfected a human melanoma cell line with the rat Hsp70-1 gene using the Tet-On system for conditional overexpression of HSP70. Induction of HSP70 did not increase cell surface expressi…

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.

Cyclosporin A mediates immunosuppression of primary cytotoxic T cell responses by impairing the release of interleukin 1 and interleukin 2

1981

The site of action of the immunosuppressive drug cyclosporin A in in vitro cytotoxic allograft responses has been localized. General cytotoxic effects of the drug on proliferating T cells became apparent at concentrations of 500-1000 ng/ml, while selective effects were observed at concentrations of 10-100 ng/ml. The selective effects included a blockade of interleukin 2 release from activated T helper cells on the one hand and inhibition of interleukin 1 release from splenic adherent cells on the other. While cyclosporin A did not interfere with the intracellular events required for the activation and subsequent clonal expansion of alloreactive T cells, the lack of interleukin 1 and interle…

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…

T cell-mediated cytotoxic immune responsiveness of chimeric mice bearing a thymus graft fully allogeneic to the graft of lymphoid stem cells

1980

Fully allogeneic, chimeric mice were established by adult thymectomy of (A × B) F1animals, grafting parental A-type thymus under the kidney capsula, followed by lethal (900 rd) irradiation and reconstitution with B parental-type bone marrow cells treated with xenogeneic anti-T cell antiserum plus complement. Following in vivo sensitization with inactivated Sendai virus (SV) suspensions, no virus-specific T cells could be detected within the spleen cells of the mice. Upon stimulation with third-party allogeneic cells in a primary mixed lymphocyte culture, spleen cells of all animals generated alloreactive cytotoxic T lymphocytes (CTL). More interestingly, upon secondary in vitro stimulation …

In Vivo Protective Effect of Tumour Necrosis Factor   Against Experimental Infection with Herpes Simplex Virus Type 1

1991

C57BL/6 mice, which differ genetically from other strains by their resistance to herpes simplex virus type 1 (HSV-1) infection, were inoculated intraperitoneally with different doses of tumour necrosis factor alpha (TNF-alpha). Mice pretreated with 100 ng, or even 10 ng, of TNF-alpha showed prolonged survival compared to control mice that were infected with 10(7) p.f.u. of HSV-1. Significant protection was observed in mice injected 4 or 8 h prior to or after HSV-1 inoculation, respectively. Protection was also observed when mice which differed at their H-2 locus were treated with TNF-alpha after infection with HSV-1. Interferon could not be detected in the sera of mice at different time poi…

Targeting positive regulatory domain I-binding factor 1 and X box-binding protein 1 transcription factors by multiple myeloma-reactive CTL.

2005

Abstract Growing evidence indicates that multiple myeloma (MM) and other malignancies are susceptible to CTL-based immune interventions. We studied whether transcription factors inherently involved in the terminal differentiation of mature B lymphocytes into malignant and nonmalignant plasma cells provide MM-associated CTL epitopes. HLA-A*0201 (A2.1) transgenic mice were used to identify A2.1-presented peptide Ag derived from the plasma cell-associated transcriptional regulators, positive regulatory domain I-binding factor 1 (PRDI-BF1) and X box-binding protein 1 (XBP-1). A2.1-restricted CTL specific for PRDI-BF1 and XBP-1 epitopes efficiently killed a variety of MM targets. PRDI-BF1- and X…

Impact of thymus on the generation of immunocompetence and diversity of antigen-specific MHC-restricted cytotoxic T-lymphocyte precursors.

1981

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-…