Publication details

Low antigen-dependent activity of T cells after repeated stimulation using dendritic cells and expansion with interleukin-2.

Authors

BÜCHLER Tomáš HÁJEK Roman KOVÁŘOVÁ Lucie MUSILOVÁ R. BOURKOVÁ L. ČECH Zbyněk VÁNOVÁ P. TŮZOVÁ L. VIDLÁKOVÁ Petra VORLÍČEK Jiří PENKA Miroslav

Year of publication 2003
Type Article in Periodical
Magazine / Source Neoplasma
MU Faculty or unit

Faculty of Medicine

Citation
Field Oncology and hematology
Keywords dendritic cell; IL-2;T cell
Description Both CD8+ and CD4+ T cells with specific activity against tumor antigens are needed for an efficient antitumor immune response. Activation and proliferation of T cells require cellular interactions including adhesion, recognition of peptides presented by MHC molecules to the T cells receptor, and costimulation. In a series of experiments we attempted to generate and expand specific T cells by repeated stimulation using antigen-loaded autologous dendritic cells (DCs). DCs were obtained from peripheral blood mononuclear cells (PBMC) in the presence of IL-4 and GM-CSF. TNF-alpha was added to induce maturation. A conjugate of myeloma idiotypic protein with keyhole limpet hemocyanin was used as antigen. Nonadherent peripheral blood mononuclear cells were cultured in the presence of II-2 and IL-7. Autologous DCs were added to the lymphocyte cultures on days 3, 10, and 17. The lymphocytes were stimulated by high concentration of IL-2 between days 21 and 27. Lymphocytes harvested on day 27 proliferated in response to antigen-loaded DC but failed to do so if less than 0.3x10(6) DCs were added for stimulation during culture. However, no cytotoxic activity against autologous DCs was detected and IFN-gamma production in the T cell cultures was low at the end of culture. In conclusion, the generation and expansion of T cells using repeated stimulation by autologous DCs is feasible but defective cytotoxic reponse of these cells occurs, possibly as a consequence of repeated frequent exposure to antigen.

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