Search results for " ACTIVATION"

In vitro study of alloreactivity and microchimerism after injection of dendritic cells and anti-CD4 monoclonal antibody in a combination of Lewis-Wis…

1998

Proteasome-inhibited dendritic cells demonstrate improved presentation of exogenous synthetic and natural HLA-class I peptide epitopes.

2004

The design and successful clinical implementation of cancer vaccines targeting the induction of T-cell mediated immunity is a rapidly evolving field that is hampered by an empirical selection of antigen and adjuvant. In particular, vaccines using defined tumor-associated peptide epitopes elicit only a restricted T-cell repertoire in a minority of patients. In this regard, vaccines comprising the whole spectrum of antigens presented by individual autologous tumors would be advantageous. In an in vitro model, we evaluated the capacity of naturally processed Epstein-Barr virus-transformed B-lymphoblastoid-cell line (LCL)-derived peptides to activate virus-specific CD8+ T cells of seropositive …

Separation of T-cell-stimulating activity from streptococcal M protein

1992

The superantigenic properties of M protein type 5 of Streptococcus pyogenes have been implicated as an important pathogenicity factor in streptococcal autoimmune diseases. Here we show that after a single purification step by affinity chromatography on immobilized albumin or fibrinogen, M protein has no mitogenic activity for T cells. We demonstrate that the superantigenicity of M proteins of type 5 and type 1 is due to contamination with the highly potent pyrogenic exotoxins of S. pyogenes in the range of 0.1 to 0.01%. These results raise a general caveat for work with these extremely active T-cell mitogens, because the mitogenicity of other streptococcal or staphylococcal proteins could b…

Stimulation of human T cells by microbial 'superantigens'.

1991

The enterotoxins and the TSST of S. aureus, the erythrogenic toxins A and C of S. pyogenes and a still uncharacterized exoprotein of M. arthritidis belong to a family of exotoxins that have in common a potent mitogenic activity for T lymphocytes of several species. These proteins stimulate CD4+ and C8+ T cells, as well as a fraction of gamma delta TCR-bearing T cells by cross-linking variable parts of the T cell antigen receptor with MHC class II molecules on accessory or target cells. They are functionally bivalent molecules having distinct interaction sites for variable parts of the TCR and for nonpolymorphic parts of the MHC class II molecule. For alpha beta TCR-bearing T cells the V bet…

Requirements for the growth of TH1 lymphocyte clones.

1990

Besides the signal generated in a T lymphocyte after triggering the T cell receptor (TcR), most lymphocytes need a "second signal" to become fully activated. The necessity and nature of the "second signal" differs between different types of T cells. At the level of CD4-positive T helper lymphocytes interleukin 1 (IL 1) serves as "second signal" for those of the TH2 subtype (IL4, 5, 6 producer) but not for those of the TH1 subtype (IL 2, IFN-gamma producer). This correlates with the absence of the IL 1 receptor at the surface of TH1 clones. We report herein the further purification of T cell stimulating factor (TSF), a soluble mediator involved in the proliferation of TH1 lymphocytes. A prep…

Different response of TH1 cells for stimulation with anti-CD3 antibodies.

1990

In this report, evidence is provided for a further subdivision of CD4+ T helper cell lines. The earlier definition of the TH1 and TH2 subtypes was confirmed by their differential response to interleukin (IL) 1. An additional subdivision of the TH1 subset was revealed when TH1 cell lines were costimulated with anti-CD3 antibodies and IL2. The IL2-induced proliferation of three of the resulting TH1 lines was blocked by anti-CD3 antibodies. By contrast, no such block was observed in a fourth TH1 cell line. In all four lines anti-CD3 triggering caused production of IL2. The block of proliferation was reversed neither by antigen-presenting cells nor by phorbol 12-myristate 13-acetate, a protein …

Depletion of alloreactive T cells via CD69: implications on antiviral, antileukemic and immunoregulatory T lymphocytes

2005

Selective depletion of alloreactive T cells from stem-cell allografts should abrogate graft-versus-host disease while preserving beneficial T cell specificities to facilitate engraftment and immune reconstitution. We therefore explored a refined immunomagnetic separation strategy to effectively deplete alloreactive donor lymphocytes expressing the activation antigen CD69 upon stimulation, and examined the retainment of antiviral, antileukemic, and immunoregulatory T cells. In addition to the CD69high T cell fraction, our studies retrieved two T cell subsets based on residual CD69 expression. Whereas, truly CD69(neg) cells were devoid of detectable alloresponses to original stimulators, CD69…

Postnatal development of functional T cell subsets in the mouse: a frequency analysis of mitogen reactive precursors of proliferating, of cytotoxic a…

1985

In order to study the postnatal development of functional T cell subsets in the mouse, a mitogen-driven limiting dilution culture system was used for a precursor frequency analysis of proliferating, of cytolytic and of IL 2-producing T cells, respectively, present in spleen and thymus of mice from neonatal to adult age. In adult mice, the majority (up to 100%) of splenic T cells was capable to respond to Concanavalin A. In contrast, an up to tenfold lower frequency of mitogen-reactive precursors was found within positively selected Thy-1+ spleen cells of neonatal mice. Within this fraction of Con A reactive neonatal T cells, there was an apparent imbalance in the CTLp/PTLp ratio within the …

Clonal analysis of human T cell activation by the Mycoplasma arthritidis mitogen (MAS)

1988

Mycoplasma arthritidis produces an as yet undefined soluble molecule (MAS) that has a potent mitogenic effect on T cells of several species. We have used cloned human cytotoxic and proliferative T lymphocytes to dissect the molecular mechanism of T cell activation by this mitogen. Reactivity to MAS is clonally expressed among T cell receptor (TcR) alpha/beta chain-expressing T cell clones of CD4+ or CD8+ phenotype, as well as CD4-8- TcR alpha/beta chain-negative T lymphocyte clones expressing the CD3-associated TcR gamma chain. MAS is able to induce cytotoxicity and/or proliferation in these T cell clones. For triggering of these T cells, regardless of their phenotype of specificity, the pr…

Enzymatic Activity of CD26 (Dipeptidylpeptidase IV) is not Required for Its Signalling Function in T Cells

1993

Abstract CD26 is a proteolytic enzyme (dipeptidylpeptidase IV) expressed on the T cell surface that defines an alternative activation signal for human T lymphocytes. Crosslinking of CD26 via monoclonal antibodies triggers proliferation and cytotoxicity in preactivated T cells. In this study, we used highly specific competitive and irreversible inhibitors of dipeptidylpeptidase IV to study the role of the enzymatic activity in activation of CD26- transfected T cells as well as of CD26-expressing normal human T cell clones. These inhibitors at concentrations that blocked up to 95% of the enzymatic activity, did not specifically inhibit T cell activation neither via TCR/CD3 nor via CD26 itself…