Delayed development of interferon-γ–producing Th1 cells in newborns.

In newborns, the sluggish appearance of one cell population means death to another, according to Lee et al. on page 2269. These results may help explain why newborns are highly susceptible to certain infections.

Newborn mice exposed to antigen respond by activating both T helper (Th)-1 and Th2 cells. Yet a second exposure causes allergy-promoting Th2 cells to thrive but microbe-fighting Th1 cells to die. Previous work by this group showed that antigen exposure during the first few days of life caused Th1 cells to express the cytokine receptor chain IL-13Rα1, a receptor not commonly found on these cells, which then teamed up with the IL-4Rα chain. The resulting heteroreceptor induced Th1 cell death when triggered by Th2-promoting IL-4 during secondary antigen exposure.

At six days of age, the authors now show, Th1 cells had a reversal of fortune. The turning point was marked by the appearance of a subset of antigen-presenting CD8α+ dendritic cells (DCs) that churned out life-saving IL-12. Giving newborns extra IL-12, which is feebly produced before day 6, or providing them with IL-12–producing DCs blunted the expression of IL-13Rα1 and rescued the Th1 cells. What delays the development of this DC population relative to other subsets remains unknown. RB