Developmental induction of human T-cell responses against Candida albicans and Aspergillus fumigatus

The origin of human T-cell responses against fungal pathogens early in life is not clearly understood. Here, we show that antifungal T-cell responses are vigorously initiated within the first years of life against lysates and peptides of Candida albicans or Aspergillus fumigatus, presented by autologous monocytes. The neonatal responding T-cell pool consists of 20 different TCR-V_β families, whereas infant and adult pools display dramatically less variability. Although we demonstrate no bias for anti-fungal IL-4 expression early in life, there was a strong bias for anti-fungal IL-17 production. Of note, only T-cells from neonates and infants show an immediate co-expression of multiple cytokines. In addition, only their T-cells co-express simultaneously transcription factors T-bet and RORγt in response to fungi and subsequently their target genes IL-17 and IFNγ. Thus, T-cells of neonates and infants are predetermined to respond quickly with high plasticity to fungal pathogens, which might give an excellent opportunity for therapeutic interventions.