Direct stimulation of T lymphocytes by immunosomes: Virus-like particles decorated with T cell receptor/CD3 ligands plus costimulatory molecules

Derdak, Sophia; Kueng, Hans J.; Leb, Victoria; Neunkirchner, Alina; Schmetterer, Klaus G.; Bielek, Edith; Majdic, Otto; Knapp, Walter; Seed, Brian; Pickl, Winfried F.

doi:10.1073/pnas.0602283103

Cited by 56 publications

(116 citation statements)

References 37 publications

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“…The control stimulator cell line was transduced with retrovirus-containing supernatant derived from cells transfected with the pBMNZ plasmid containing the lac Z gene. T-cell stimulator cells that are based on Bw5147 (referred to as Bw cells), a murine thymoma cell line expressing a membrane-bound single chain fragment of the variable regions of the anti-CD3 antibody (mb-aCD3scFv of clone OKT3 [38]) at high density, have been described previously [15]. Expression constructs encoding myc-tagged 4-1BBL, OX40, CD70, GITRL and CD30L were made by generating PCR fragments with forward primers specific for the N-terminal end of the molecule and reverse primers specific for the myc-tag and the transmembrane domain of the TNF family molecule.…”

Section: Generation Of T-cell Stimulator Cellsmentioning

confidence: 99%

The capacity of the TNF family members 4‐1BBL, OX40L, CD70, GITRL, CD30L and LIGHT to costimulate human T cells

et al. 2008

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Activating signals generated by members of the tumour necrosis factor receptor superfamily upon interaction with their cognate ligands play important roles in T-cell responses. Members of the tumour necrosis factor family namely 4-1BBL, OX40L, CD70, GITRL, LIGHT and CD30L have been described to function as costimulatory molecules by binding such receptors on T cells. Using our recently described system of T-cell stimulator cells we have performed the first study where all these molecules have been assessed and compared regarding their capacity to costimulate proliferation and cytokine production of human T cells. 4-1BBL, which we found to be the most potent molecule in this group, was able to mediate sustained activation and proliferation of human T cells. OX40L and CD70 were also strong inducers of T-cell proliferation, whereas the costimulatory capacity of human GITRL was significantly lower. Importantly CD30L and LIGHT consistently failed to act costimulatory on human T cells, and we therefore suggest that these molecules might be functionally distinct from the costimulatory members of this family.Key words: Cell activation . Costimulation . Costimulatory molecules . T cells IntroductionEfficient T-cell activation requires two different signals, provided by MHC-TCR interaction (signal 1) and additional receptorligand interactions that give a costimulatory signal (signal 2) to T cells [1]. Interaction of the immunoglobulin superfamily members CD80/86-CD28 and ICOSL-ICOS can efficiently costimulate proliferation, cytokine production and effector cell generation of T cells [2]. Another group of costimulatory molecules is comprised by members of the tumour necrosis factor receptor (TNFR) superfamily, which can costimulate TCR signals upon interaction with their cognate ligands, members of TNF super-family. Costimulation of T-cell activation has been reported for several members of the TNFR/TNF superfamilies namely for 4-1BB-4-1BBL, OX40-OX40L, CD27-CD70, GITR-GITRL, herpes virus entry mediator (HVEM)-LIGHT and 2678CD30-CD30L [3,4]. Interaction of these TNF family ligands with their receptors leads to recruitment of TNFR-associated factors (TRAF), which initiate signalling cascades that result in T-cell activation. All these TNFR can recruit TRAF2 but there are differences between these molecules in the recruitment of other TRAF proteins [5].Although there is extensive literature on costimulatory pathways involving human 4-1BBL, OX40L and CD70, few reports have described costimulatory functions for human LIGHT and CD30L [6,7]. Signals transduced by members of the TNFR family are regarded as especially important for survival, expansion and effector function of T cells that have initially received activating signals via the CD28 receptor [4]. Consequently a number of reports have addressed the role of members of the TNFR/TNF families on antigen-experienced T cells and have demonstrated potent and important costimulatory functions for these molecules on virus-specific human T cells [8][9][10][11]. Thus blocking or ...

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Section: Generation Of T-cell Stimulator Cellsmentioning

confidence: 99%

The capacity of the TNF family members 4‐1BBL, OX40L, CD70, GITRL, CD30L and LIGHT to costimulate human T cells

et al. 2008

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“…A stable transfectant of the 293 cell line expressing a single-chain variable fragment (scFv) of the CD3ε-specific hybridoma OKT3 attached to the CD14 molecule (OKT3scFv::GPI) was established and grown in the presence of 1 g/ml of puromycin (Sigma Chemicals, St. Louis, MO) as described elsewhere (16). Peripheral blood mononuclear cells (PBMC) were isolated from heparinized blood of healthy adult donors upon informed consent by standard density gradient centrifugation with Lymphoprep (Technoclone, Vienna, Austria).…”

Section: Cell Lines and Primary Cellsmentioning

confidence: 99%

General Strategy for Decoration of Enveloped Viruses with Functionally Active Lipid-Modified Cytokines

Kueng

Leb

Haiderer

et al. 2007

J Virol

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Viral particles preferentially incorporate extra-and intracellular constituents of host cell lipid rafts, a phenomenon central to pseudotyping. Based on this mechanism, we have developed a system for the predictable decoration of enveloped viruses with functionally active cytokines that circumvents the need to modify viral proteins themselves. Human interleukin-2 (hIL-2), hIL-4, human granulocyte-macrophage colony-stimulating factor (hGM-CSF), and murine IL-2 (mIL-2) were used as model cytokines and fused at their C terminus to the glycosylphosphatidylinositol (

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“…In this way, the functional activity of artificial APC can be modulated by modifying the composition of the expressed molecules. Although several artificial systems have been produced, [13][14][15][16][17][18][19][20][21][22][23][24] only the following systems are suitable for clinical use, having been generated under conditions of Good Manufacturing Practice: immunomagnetic beads coated with anti-CD3 and anti-CD28 monoclonal antibodies (mAb) 25,26 and anti-CD3 mAb immobilized on culture plates. Although this technology can efficiently support the expansion of CD4 + T cells, 27 the long-term growth of purified CD8 + T cells is hampered.…”

Section: Introductionmentioning

confidence: 99%

The effect of artificial antigen-presenting cells with preclustered anti-CD28/-CD3/-LFA-1 monoclonal antibodies on the induction of ex vivo expansion of functional human antitumor T cells

Zappasodi¹,

Nicola²,

Carlo‐Stella³

et al. 2008

Haematologica

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BackgroundAdoptive cell therapy with ex vivo expanded autologous antitumor cytotoxic T lymphocytes represents an important therapeutic option as an anticancer strategy. In order to identify a reliable method for producing adequate amounts of functional antitumor cytotoxic T lymphocytes with a potentially long in vivo lifespan, we tested the T-cell expansion efficiency of a new artificial antigen-presenting cell-based system.

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Direct stimulation of T lymphocytes by immunosomes: Virus-like particles decorated with T cell receptor/CD3 ligands plus costimulatory molecules

Cited by 56 publications

References 37 publications

The capacity of the TNF family members 4‐1BBL, OX40L, CD70, GITRL, CD30L and LIGHT to costimulate human T cells

The capacity of the TNF family members 4‐1BBL, OX40L, CD70, GITRL, CD30L and LIGHT to costimulate human T cells

General Strategy for Decoration of Enveloped Viruses with Functionally Active Lipid-Modified Cytokines

The effect of artificial antigen-presenting cells with preclustered anti-CD28/-CD3/-LFA-1 monoclonal antibodies on the induction of ex vivo expansion of functional human antitumor T cells

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