Further experiments involving studies in rhesus macaques will be required
to find optimal adjuvant formulations able to specifically shape protective immune CCI-779 responses to a given pathogen. In conclusion, the findings reported here contribute to our knowledge about rhesus macaque B-cell responses and support the relevance of using non-human primates for modelling TLR-administration to people. These data will hopefully inform future vaccine design and development of adjuvant strategies. This work was supported by grants from Vetenskapsradet, the Swedish International Development Agency (Sida), the International AIDS Vaccine Initiative (IAVI), the Swedish Governmental Agency for Innovation Systems (Vinnova) and the Swedish Society of Medicine. We are grateful for the assistance of the veterinarians Drs Mats Spångberg and Helene Fredlund, and to the personnel at the Astrid Fagraeus Laboratory
at the Swedish Institute for Infectious Disease Control. The authors have no financial conflicts of interest. “
“α-Fetoprotein (AFP) is a tumour-associated antigen in hepatocellular carcinoma (HCC). The biological properties of AFP have been identified in its regulatory effects on immune responses of T cells and B cells. However, AFP effects on natural killer (NK) cells are still unclear. In this study, we examined the immunoregulation of AFP on NK activity. The cytolytic activity against K562 cells and Huh7 cells Selleck MI-503 of NK cells co-cultured
with AFP-treated dendritic cells (DCs) (AFP-DCs) was lower than that with albumin-treated DCs (Alb-DCs). Direct addition of AFP to NK cells did not alter the cytolytic activity of NK cells. Adding AFP inhibited the interleukin (IL)-12 production of DCs after stimulation with lipopolysaccharide (LPS) [Toll-like receptor (TLR)-4 ligand], Progesterone or Poly(I:C) (TLR-3 ligand), but not IL-18 production. The mRNAs of IL-12p35 and IL-12p40 were significantly inhibited in AFP-DCs compared with Alb-DCs, but those of TLR-4 or TLR-3 were not. Transwell experiments revealed that soluble factors derived from DCs played roles in inhibition of the ability of activating NK cells by AFP-DCs. Adding the neutralizing antibody of IL-12 to NK cells co-cultured with Alb-DCs resulted in a decrease of cytolytic activity to the levels of NK cells co-cultured with AFP-DCs. Adding IL-12 to NK cells co-cultured with AFP-DCs resulted in an increase of cytolytic activity to the levels of NK cells co-cultured with Alb-DCs. These demonstrated that the impairment of IL-12 production from AFP-DCs resulted in inhibition of the ability of the activation of NK cells by DCs, and thus suggests a role of AFP in HCC development. Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide.