A Practical Approach, Second Edition=Ronald D. Ho.pdf

POSTNATAL DEVELOPMENTAL MILESTONES 1087lymphoid thymocytes which express the TcR and the TcR-specific cell surface proteins, CD3, CD4and CD8. Thymic cell production wanes rapidly following sexual maturity resulting in the virtualabsence of thymocyte production at one year of life in mice (Shortman et al., 1998).RatsLess is known about thymus development in the rat. The thymus anlage in rats is invaded byhematopoietic stem cells by day 13 of gestation, and these cells have differentiated to express bothCD4 and CD8 (e.g., double positive cells) by day 18 (Aspinall et al., 1991). Mature single positivethymocytes are not detected until day 21 in the rat.DogsThe primordia of the thymus is evident in dogs between days 27 and 28, and it descends from thecervical region into the anterior thoracic cavity on day 35 (Kelly, 1963; Felsberg, 1998). At this time,the thymus is composed of epithelial lobules and mesenchymal stroma only. Between days 35-40, thefetal thymus becomes actively lymphopoietic and shows corticomedullary demarcation; by day 45 thethymic microenvironment has assumed its normal postnatal histologic appearance (Miller and Benjamin,1985; Snyder et al., 1993; Felsberg, 1998). Fetal and postnatal thymopoiesis has been recentlyevaluated in dogs and the results indicate that normal thymopoiesis is occurring by day 45 of gestationwith a distribution of thymocyte subsets virtually identical to that seen in the postnatal thymus, althoughwith a markedly reduced total cellularity (Somberg et al., 1994; Felsberg, 1998). The thymus undergoesrapid postnatal growth and reaches maximum size at 1 to 2 months of age, as the percentage of bodyweight, and at 6 months of age in absolute terms (Yang and Gawlak, 1989).PrimatesFetal thymic histogenesis in primates (rhesus) has been demonstrated to be gradual and continuous,as is the case in humans (Tanimura and Tanioka, 1975). The thymic anlage separates from thepharyngeal pouches and engages in early stages of proliferation at gestation days 37 – 48 (Hendrickxet al., 1975). These same studies showed that the differentiation of lymphoid elements occurredwithin the thymus at gestation days 50 – 73; and the maturation of the fetal lymphoid systemoccurred at gestation days 100 – 133. Later studies by the same laboratory using another speciesof primates (cynomolgus) indicated that the cortex and medulla of the thymus were distinguishableby gestational day 65, and most of the thymocytes were CD3 + and localized throughout both regionsof the fetal thymus, while CD20 + B-cells were dispersed in the corticomedullary junction. In olderfetuses (gd 100 and gd 145), CD20 + B-cells increased in the medulla and corticomedullary junction,while the number of CD3 + thymocytes remained similar throughout gestation (Hendrickx et al.,2002). In the same study, flow cytometric analysis of lymphocyte subsets indicated a slight increasein the single positive (CD4 + /CD8 - and CD4 - /CD8 + ) thymocytes and a slight decrease (86% to 76%)in double positive (CD4 + /CD8 + ) thymocytes between gestational days 80 and 145.Bone Marrow HematopoiesisThe final critical stage in the embryonic development of the mammalian immune system is theestablishment of the bone marrow as the primary hematopoietic organ.HumansBone marrow lymphopoiesis begins in the human fetus at approximately week 12 (West, 2002).B-lymphocyte development begins at approximately the same time as T-cells in humans. B-cells© 2006 by Taylor & Francis Group, LLC