Tolerogenic dendritic cells impede priming of naive CD 8 super(+) T cells and deplete memory CD 8 super(+) T cells

Type 1 diabetes is a T -cell-mediated autoimmune disease in which autoreactive CD 8 super(+) T cells destroy the insulin-producing pancreatic beta cells. Vitamin D 3 and dexamethasone-modulated dendritic cells ( C ombi- DC s) loaded with islet antigens inducing islet-specific regulatory CD 4 super(+) T cells may offer a tissue-specific intervention therapy. The effect of C ombi- DC s on CD 8 super(+) T cells, however, remains unknown. To investigate the interaction of CD 8 super(+) T cells with C ombi- DC s presenting epitopes on HLA class I, naive, and memory CD 8 super(+) T cells were co-cultured with DC s and proliferation and function of peptide-specific T cells were analyzed. Antigen-loaded C ombi- DC s were unable to prime naive CD 8 super(+) T cells to proliferate, although a proportion of T cells converted to a memory phenotype. Moreover, expansion of CD 8 super(+) T cells that had been primed by mature monocyte-derived DC s (mo DC s) was curtailed by C ombi- DC s in co-cultures. C ombi- DC s expanded memory T cells once, but CD 8 super(+) T -cell numbers collapsed by subsequent re-stimulation with C ombi- DC s. Our data point that (re)activation of CD 8 super(+) T cells by antigen-pulsed C ombi- DC s does not promote, but rather deteriorates, CD 8 super(+) T -cell immunity. Yet, C ombi- DC s pulsed with CD 8 super(+) T -cell epitopes also act as targets of cytotoxicity, which is undesirable for survival of C ombi- DC s infused into patients in therapeutic immune intervention strategies.