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.

中文翻译：

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早期 T-Helper 1 免疫

这篇简短的评论是为了纪念 Eli Sercarz，他是一位同事，在众多成就中，他开创并振兴了与儿童健康高度相关的早期免疫领域。长期以来，新生儿阶段被视为暴露于抗原 (Ag) 诱导免疫耐受的窗口。然而，在 1990 年初，人们发现在出生当天给予 Ag 的新生小鼠在随后用相同的 Ag 攻击时会产生免疫力。但是，这些二次反应显示出 T 辅助 (Th)1 细胞和过量 Th2 淋巴细胞的缺陷。这些发现解释了在新生儿阶段给予 Ags 的感知耐受性，并将有效的新生儿疫苗的缺乏与过敏反应的脆弱性相关联。分析新生儿 Th1 细胞缺陷的机制揭示了 Ag 呈递细胞与其产生的细胞因子之间复杂的发育相互作用。这最终导致环境中的白细胞介素 (IL)-12 有限，并上调 IL-13Rα1 表达及其与 Th1 细胞表面的 IL-4Rα 的关联。Ag 重新暴露后，Th2 细胞产生 IL-4 和 -13。两者都与 Th1 细胞表面的异源受体结合并引发它们的死亡。通常，细胞因子促进 T 细胞的生长，但在这种情况下，IL-4 和 -13 会刺激干扰素调节因子 1 (IRF-1) 的产生。IRF-1 从细胞核转移到细胞质并刺激终止 Th1 细胞的凋亡机制。这表明可以提高 IL-12 产生的疫苗制剂可能会对抗 IL-13Rα1 表达，