Adjuvants LT-K63 and CpG enhance the activation of dendritic cells in neonatal mice

Abstract

Dendritic cells (DC) play a major role in the priming of T cells and initiating specific immune responses. We assessed the effects of the adjuvants LT-K63 and CpG on neonatal DC in vivo and in vitro. Cytokine levels (IL-10, IL-12p70 and IL-12p40/IL-23p40) were measured and the expression of the activation markers CD86, CD40 and MHCII on CD11c+ DC was analysed by using FACS. The proportion of MHCII high CD11c+ DC was higher in neonatal mice immunized with a pneumococcal conjugate (PncTT) and LT-K63 or CpG compared with that when PncTT was alone. In vitro stimulation with LT-K63 enhanced the expression of CD86 more on CD11c+ DC from spleens of mice immunized as neonates than those immunized as adults, whereas in vitro stimulation with CpG enhanced the expression of CD86 and CD40 on CD11c+ DC similarly in both age groups. CpG stimulation in vitro enhanced IL-10 and IL-12(p70) production in mice immunized as neonates with PncTT and either adjuvant, but not PncTT alone. The adjuvants LT-K63 and CpG enhance the activation of CD11c+ DC in mice immunized as neonates and can thereby overcome one of the limiting factors in the initiation of the immune response to conjugate vaccines in early life. The fact that neonatal DC are more susceptible to stimulation with either adjuvant, LT-K63 or CpG, could imply that neonatal CD11c+ DC are more easily activated than adult CD11c+ DC, and /or be a consequence of the predominance of different DC subsets in neonatal and adult mice.