Gastrointestinal viral infections are a major global cause of disease and mortality in infants. Cytotoxic CD8⁺ T cells are critical to achieve viral control. However, studies investigating the development of CD8⁺ T cell immunity in human tissues early in life are lacking. Here, we investigated the maturation of the CD8⁺ T cell compartment in human fetal, infant and adult intestinal tissues. CD8⁺ T cells exhibiting a memory phenotype were already detected in fetal intestines and increased after birth. Infant intestines preferentially harbored effector CCR7⁻CD45RA⁻CD127⁻KLRG1^+/− CD8⁺ T cells compared to tissue-resident memory CD69⁺CD103⁺CD8⁺ T cells detected in adults. Functional cytotoxic capacity, including cytokine and granzyme B production of infant intestinal effector CD8⁺ T cells was, however, markedly reduced compared to adult intestinal CD8⁺ T cells. This was in line with the high expression of the inhibitory molecule PD-1 by infant intestinal effector CD8⁺ T cells. Taken together, we demonstrate that intestinal CD8⁺ T cell responses are induced early in human development, however exhibit a reduced functionality. The impaired CD8⁺ T cell functionality early in life contributes to tolerance during foreign antigen exposure after birth, however functions as an immune correlate for the increased susceptibility to gastrointestinal viral infections in infancy.

胃肠道病毒感染是全球婴儿疾病和死亡的主要原因。细胞毒性 CD8 ⁺ T 细胞对于实现病毒控制至关重要。然而，缺乏调查生命早期人体组织中CD8 ^{+ T 细胞免疫力发展的研究。}在这里，我们研究了人类胎儿、婴儿和成人肠道组织中 CD8 ⁺ T 细胞区室的成熟。表现出记忆表型的CD8 ⁺ T 细胞已在胎儿肠道中检测到，并在出生后增加。婴儿肠道优先携带效应子 CCR7 ⁻ CD45RA ⁻ CD127 ⁻ KLRG1 ^+/− CD8 ⁺T 细胞与在成人中检测到的组织驻留记忆 CD69 ⁺ CD103 ⁺ CD8 ^{+ T 细胞相比。然而，与成人肠道 CD8 +} T 细胞相比，婴儿肠道效应 CD8 ⁺ T 细胞的功能性细胞毒性能力（包括细胞因子和颗粒酶 B 的产生）显着降低。^{这与婴儿肠道效应 CD8 +} T 细胞高表达抑制分子 PD-1 一致。总之，我们证明肠道 CD8 ⁺ T 细胞反应在人类发育早期被诱导，但表现出功能降低。受损的CD8 ⁺生命早期的 T 细胞功能有助于提高出生后外来抗原暴露期间的耐受性，但与婴儿期胃肠道病毒感染易感性增加的免疫相关。