Hendrickx A G, Makori N, Peterson P
California Regional Primate Research Center, University of California, Davis, California 95616-8542, USA.
Hum Exp Toxicol. 2002 Sep-Oct;21(9-10):537-42. doi: 10.1191/0960327102ht294oa.
Macaques are well suited for preclinical testing of biopharmaceutics due to reproductive and developmental similarities with humans. In order to characterize ontogeny of the immune system in this model, we studied lymphocyte and antigen-presenting cell populations in developing lymphoid tissues of rhesus macaque fetuses during the second and third trimesters [gestation days (GD) 75-145, term 165 days]. Systemic lymphoid tissues (thymus, spleen and lymph nodes, and intestinal tissue) were examined for morphology and cell surface markers by immunohistochemistry. Lymphocytes were further characterized by flow cytometry for differentiation markers. Splenic tissue from early second trimester fetuses was populated mainly by CD20+ B cells while the thymus contained large numbers of CD3+ T cells. In the late second trimester (day 80), approximately equal populations of B and T cells were present in both tissues and numerous dendritic cells (p55+) were present in the intestinal lamina propria. By the second trimester, the rhesus macaque fetal lymphoid system is well developed. Analysis of lymphoid organs from retinoic acid-treated fetuses indicated that the T-cell (thymus)-dependent compartment of the spleen white pulp in specimens with thymic aplasia showed a reduction in size and proportion of CD3+ T cells compared to controls. Our findings indicate that RA-induced thymic defects result in disrupted development of the splenic T-cell-dependent compartment.
由于猕猴在生殖和发育方面与人类相似，因此非常适合生物制药的临床前测试。为了描述该模型中免疫系统的个体发育，我们研究了恒河猴胎儿在妊娠中期和晚期（妊娠天数[GD]75 - 145天，足月为165天）发育中的淋巴组织中的淋巴细胞和抗原呈递细胞群体。通过免疫组织化学检查全身淋巴组织（胸腺、脾脏、淋巴结和肠道组织）的形态和细胞表面标志物。通过流式细胞术进一步表征淋巴细胞的分化标志物。妊娠中期早期胎儿的脾脏组织主要由CD20 + B细胞组成，而胸腺中含有大量CD3 + T细胞。在妊娠中期晚期（第80天），两种组织中B细胞和T细胞的数量大致相等，并且在肠固有层中存在大量树突状细胞（p55 +）。到妊娠中期，恒河猴胎儿淋巴系统发育良好。对维甲酸处理的胎儿的淋巴器官分析表明，与对照组相比，胸腺发育不全标本中脾脏白髓的T细胞（胸腺）依赖性区域的大小和CD3 + T细胞比例降低。我们的研究结果表明，维甲酸诱导的胸腺缺陷导致脾脏T细胞依赖性区域的发育中断。
