Early life environmental exposure, particularly during perinatal period, can have a life-long impact on organismal development and physiology. The biological rationale for this phenomenon is to promote physiological adaptations to the anticipated environment based on early life experience. However, perinatal exposure to adverse environments can also be associated with adult-onset disorders. Multiple environmental stressors induce glucocorticoids, which prompted us to investigate their role in developmental programming. Here, we report that perinatal glucocorticoid exposure had long-term consequences and resulted in diminished CD8 T cell response in adulthood and impaired control of tumor growth and bacterial infection. We found that perinatal glucocorticoid exposure resulted in persistent alteration of the hypothalamic-pituitary-adrenal (HPA) axis. Consequently, the level of the hormone in adults was significantly reduced, resulting in decreased CD8 T cell function. Our study thus demonstrates that perinatal stress can have long-term consequences on CD8 T cell immunity by altering HPA axis activity.

生命早期环境暴露，尤其是围产期，会对机体发育和生理产生终生影响。这种现象的生物学原理是根据早期生活经验促进对预期环境的生理适应。然而，围产期暴露于不利环境也可能与成人发病有关。多种环境压力源诱导糖皮质激素，这促使我们研究它们在发育规划中的作用。在这里，我们报告围产期糖皮质激素暴露会产生长期后果，并导致成年期 CD8 T 细胞反应减弱以及对肿瘤生长和细菌感染的控制受损。我们发现围产期糖皮质激素暴露导致下丘脑-垂体-肾上腺 (HPA) 轴的持续改变。因此，成人体内的激素水平显着降低，导致 CD8 T 细胞功能下降。因此，我们的研究表明，围产期压力可通过改变 HPA 轴活性对 CD8 T 细胞免疫产生长期影响。