This brief review is written in memory of Eli Sercarz, a colleague who among many achievements, pioneered and revitalized early-life immunity, a field that is of high relevance to child health. For a long time, the neonatal stage was viewed as a window during which exposure to antigen (Ag) induces immune tolerance. In early 1990, however, it was discovered that the newborn mouse given Ag on the day of birth develops immunity when challenged later with the same Ag. But, these secondary responses displayed a deficit in T-helper (Th)1 cells and excess Th2 lymphocytes. Such discoveries explain the perceived tolerance of Ags given at the neonatal stage and correlate the paucity of effective neonatal vaccines and vulnerability to allergic reactions. Analyzing the mechanisms underlying neonatal Th1 cell deficits revealed a complex developmental interaction between Ag-presenting cells and the cytokines that they produced. This culminated into limited interleukin (IL)-12 in the environment and up-regulation of IL-13Rα1 expression and its association with IL-4Rα on the surface of Th1 cells. After Ag re-exposure, Th2 cells produce IL-4 and -13. Both bind to the heteroreceptor on Th1 cell surfaces and trigger their death. Usually, cytokines promote growth of T cells, but in this case IL-4 and -13 stimulate production of interferon regulatory factor 1 (IRF-1). IRF-1 translocates from nucleus to cytoplasm and stimulates apoptotic machinery that terminates Th1 cells. This suggests that vaccine formulations that could elevate IL-12 production are likely to counter IL-13Rα1 expression, preserve Th1 cells, and potentiate vaccine efficacy in neonates.