Epitopes described in "Tolerogenic dendritic cells impede priming of naïve CD8⁺ T cells and deplete memory CD8⁺ T cells."

Article Authors:Fleur S Kleijwegt; Diahann T S L Jansen; Josefine Teeler; Antoinette M Joosten; Sandra Laban; Tatjana Nikolic; Bart O Roep
Article Title:Tolerogenic dendritic cells impede priming of naïve CD8⁺ T cells and deplete memory CD8⁺ T cells.
Reference Detail
Reference ID:1025428
Abstract:Type 1 diabetes is a T-cell-mediated autoimmune disease in which autoreactive CD8(+) T cells destroy the insulin-producing pancreatic beta cells. Vitamin D3 and dexamethasone-modulated dendritic cells (Combi-DCs) loaded with islet antigens inducing islet-specific regulatory CD4(+) T cells may offer a tissue-specific intervention therapy. The effect of Combi-DCs on CD8(+) T cells, however, remains unknown. To investigate the interaction of CD8(+) T cells with Combi-DCs presenting epitopes on HLA class I, naive, and memory CD8(+) T cells were co-cultured with DCs and proliferation and function of peptide-specific T cells were analyzed. Antigen-loaded Combi-DCs were unable to prime naïve CD8(+) T cells to proliferate, although a proportion of T cells converted to a memory phenotype. Moreover, expansion of CD8(+) T cells that had been primed by mature monocyte-derived DCs (moDCs) was curtailed by Combi-DCs in co-cultures. Combi-DCs expanded memory T cells once, but CD8(+) T-cell numbers collapsed by subsequent re-stimulation with Combi-DCs. Our data point that (re)activation of CD8(+) T cells by antigen-pulsed Combi-DCs does not promote, but rather deteriorates, CD8(+) T-cell immunity. Yet, Combi-DCs pulsed with CD8(+) T-cell epitopes also act as targets of cytotoxicity, which is undesirable for survival of Combi-DCs infused into patients in therapeutic immune intervention strategies.
Reference Type:Literature
PubMed ID:23042025
Journal:Eur J Immunol
Journal Volume:43
Article Pages:85-92
Journal ISSN:0014-2980
Article Chemical List:Epitopes, T-Lymphocyte;HLA Antigens;Cholecalciferol;Dexamethasone
Article MeSH List:CD8-Positive T-Lymphocytes(immunology); Cell Differentiation; Cell Proliferation; Cells, Cultured; Cholecalciferol(immunology); Clonal Deletion; Coculture Techniques; Cytotoxicity, Immunologic; Dendritic Cells(immunology; transplantation); Dexamethasone(immunology); Diabetes Mellitus, Type 1(immunology; therapy); Epitopes, T-Lymphocyte(immunology; metabolism); HLA Antigens(metabolism); Humans; Immune Tolerance; Immunologic Memory; Lymphocyte Activation; Lymphocyte Depletion; T-Lymphocyte Subsets(immunology)
Curation Last Updated:2014-10-03 22:50:55