Weitkamp Jörn-Hendrik, Rudzinski Erin, Koyama Tatsuki, Correa Hernan, Matta Pranathi, Alberty Brannon, Polk D-Brent
Department of Pediatrics, Division of Neonatology, Monroe Carell Jr. Children's Hospital at Vanderbilt, 2215 B Garland Avenue, 1125 MRB IV/Light Hall, Nashville, TN 37232-0656, USA.
Pediatr Dev Pathol. 2009 Nov-Dec;12(6):443-9. doi: 10.2350/08-09-0533.1.
FOXP3(+) regulatory T cells (Treg) suppress innate and adaptive immune responses and are critical for intestinal immune homeostasis. Our objective was to define the postnatal developmental regulation of Treg in relationship to other T cells in the human intestinal tract. We analyzed 41 small and 18 large intestinal paraffin-embedded tissue samples from preterm and term infants with and without necrotizing enterocolitis (NEC) for the presence of CD3(+), CD4(+), CD8(+), and FOXP3(+) cells by immunohistochemistry. We compared labeled cells against age, gestational age (GA), or (corrected) postmenstrual age (PMA). The GA ranged from 23 to 40 weeks, with a mean of 32 (standard deviation, 4.7) weeks. Independent of age, GA, or PMA, the numbers of CD4(+) cells were higher in the small intestine compared to the large intestine (P = 0.046), except in patients with NEC. FOXP3(+) cells could be detected as early as 23 weeks in GA in both large and small bowel, and similar quantities were detected at the highest GA examined (40 weeks). We saw no statistically significant effect of GA, age, or PMA on total number of FOXP3(+) cells or by comparing FOXP3(+) to CD4(+) or FOXP3(+) to CD8(+) ratios, indicating intact ontogeny of Treg in intestinal tissue early in gestation. Human infants exhibit presence of mucosal FOXP3(+) cells in the small and large intestinal mucosa at birth and as early as 23 weeks GA. The frequency of FOXP3(+) cells and the ratios of FOXP3(+) to CD4(+) or CD8(+) cells do not change with increasing intrauterine development or postnatal age.
叉头框蛋白3（FOXP3）阳性调节性T细胞（Treg）可抑制先天性和适应性免疫反应，对肠道免疫稳态至关重要。我们的目标是确定人类肠道中Treg与其他T细胞相关的出生后发育调控情况。我们通过免疫组织化学分析了41份来自早产和足月婴儿、有或无坏死性小肠结肠炎（NEC）的小肠和18份大肠石蜡包埋组织样本中CD3(+)、CD4(+)、CD8(+)和FOXP3(+)细胞的存在情况。我们将标记细胞与年龄、胎龄（GA）或（校正后的）月经龄（PMA）进行比较。GA范围为23至40周，平均为32（标准差，4.7）周。与年龄、GA或PMA无关，除了患有NEC的患者外，小肠中CD4(+)细胞的数量高于大肠（P = 0.046）。在GA为23周时，在大肠和小肠中均可最早检测到FOXP3(+)细胞，并且在检查的最高GA（40周）时检测到的数量相似。我们未发现GA、年龄或PMA对FOXP3(+)细胞总数有统计学显著影响，也未发现通过比较FOXP3(+)与CD4(+)或FOXP3(+)与CD8(+)比率有统计学显著影响，这表明妊娠早期肠道组织中Treg的个体发生是完整的。人类婴儿在出生时以及早在GA为23周时，在小肠和大肠黏膜中就存在黏膜FOXP3(+)细胞。FOXP3(+)细胞的频率以及FOXP3(+)与CD4(+)或CD8(+)细胞的比率不会随着子宫内发育或出生后年龄的增加而改变。
