Tolerogenic dendritic cells impede priming of naïve CD8+ T cells and deplete memory CD8+ T cells. Issue 1 (12th November 2012)

• Record Type: Journal Article
• Authors: Kleijwegt, Fleur S.; Jansen, Diahann T. S. L.; Teeler, Josefine; Joosten, Antoinette M.; Laban, Sandra; Nikolic, Tatjana; Roep, Bart O.
• Is Part Of: European journal of immunology. Volume 43:Issue 1(2013:Jan.)
• Page Start: 85
• Page End: 92
• Publication Date: 2012-11-12
• Subjects: Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201242879
• Languages: English
• ISSNs: 0014-2980

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Type 1 diabetes is a T‐cell‐mediated autoimmune disease in which autoreactive CD8<sup>+</sup> 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<sup>+</sup> T cells may offer a tissue‐specific intervention therapy. The effect of Combi‐DCs on CD8<sup>+</sup> T cells, however, remains unknown. To investigate the interaction of CD8<sup>+</sup> T cells with Combi‐DCs presenting epitopes on HLA class I, naive, and memory CD8<sup>+</sup> 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<sup>+</sup> T cells to proliferate, although a proportion of T cells converted to a memory phenotype. Moreover, expansion of CD8<sup>+</sup> 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<sup>+</sup> T‐cell numbers collapsed by subsequent re‐stimulation with Combi‐DCs. Our data point that (re)activation of CD8<sup>+</sup> T cells by antigen‐pulsed Combi‐DCs does not promote, but rather deteriorates, CD8<sup>+</sup> T‐cell immunity. Yet, Combi‐DCs pulsed with CD8<sup>+</sup> 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.</p> </abstract>