Unbalanced Neonatal CD4(+) T-Cell Immunity

Abstract

In comparison to adults, newborns display a heightened susceptibility to pathogens and a propensity to develop allergic diseases. Particular properties of the neonatal immune system can account for this sensitivity. Indeed, a defect in developing protective Th1-type responses and a skewing toward Th2 immunity characterize today the neonatal T-cell immunity. Recently, new findings concerning Th17, regulatory helper T-cell, and follicular helper T-cell subsets in newborns have emerged. In some circumstances, development of effector inflammatory Th17-type responses can be induced in neonates, while differentiation in regulatory T-cells appears to be a default program of neonatal CD4(+) T-cells. Poor antibody production, affinity maturation, and germinal center reaction in vaccinated neonates are correlated with a limiting expansion of TFH lymphocytes. We review herein the factors accounting for and the implications of the unbalanced neonatal helper T-cell immunity.

Keywords: T helper subsets; Th17; Th2-biased response; Tregs; defective Th1 response; follicular helper T-cells; vaccine.

Figure 1

CD4⁺ T-cell differentiation in early life. Defect in Th1, Th17, and TFH differentiation and enhanced Th2 and Treg differentiation characterize the neonatal T-cell immunity. At the molecular level, respective transcriptional factors and cytokines are positively (bold) or negatively (italic) regulated. Implications of this unbalanced adaptive immunity are depicted.