| In order to maintain the balance between immunity and tolerance, dendritic cells (DC), a highly specialised population of white blood cells, play an important role. The use of DC for the generation of anti-tumour immunity is currently a popular track for the development of cellular anti-tumour vaccines. Cervical cancer is caused by infection with the human papillomavirus (HPV). In this study, we developed and validated a DC-based immunotherapy for stimulation of cellular immunity against HPV type 16 (HPV-16). We can detect a tumour antigen-specific cellular immune response in 5/5 healthy volunteers. However, the cultivation protocol was rather time-consuming and suboptimal as multiple rounds of in vitro stimulation with tumour antigen-loaded DC were necessary. Moreover, stimulation of tumour antigen-specific T-cells was only possible using purified CD8+ T-cells. These obstacles suggested the influence of other (T) cell populations capable of suppressing anti-tumour immunity. Therefore, research towards a better understanding of the cellular interactions as well as the mechanisms involved in immunity as well as tolerance, is warranted.; A major role in controlling both immunity and tolerance is also attributed to regulatory T-cells (Treg). While Treg in normal conditions regulate ongoing immune responses and prevent immunity, imbalanced function of these Treg might lead to decreased immunity or autoimmunity. We demonstrated that in vitro culture of peripheral blood lymphocytes (PBL) with both immature and mature DC resulted in an increase in the number of Treg with an increased expression of immune suppressive cytokines. In addition, the suppressive capacity of this CD4+ T-cell population was transferable to already activated antigen-specific CD8+ T-cells when CD4+ T-cells were conditioned by immature DC and cytokine cocktail-matured DC, but not when CD4+ T-cells were conditioned by Toll-like receptor (TLR)3 ligand-matured DC. |
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