Tolerogenic dendritic cells impede priming of naïve CD8+T cells and deplete memory CD8+T cells
Autor: | Diahann T. S. L. Jansen, Tatjana Nikolic, Fleur S. Kleijwegt, Bart O. Roep, Sandra Laban, Josefine Teeler, Antoinette M. Joosten |
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Rok vydání: | 2012 |
Předmět: |
0303 health sciences
CD40 biology Immunology CD28 hemic and immune systems chemical and pharmacologic phenomena Natural killer T cell 3. Good health 03 medical and health sciences Interleukin 21 0302 clinical medicine Interleukin 12 biology.protein Immunology and Allergy Cytotoxic T cell IL-2 receptor Antigen-presenting cell 030304 developmental biology 030215 immunology |
Zdroj: | European Journal of Immunology. 43:85-92 |
ISSN: | 0014-2980 |
Popis: | 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 naive 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. |
Databáze: | OpenAIRE |
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