Immunological Tolerance During Fetal Development: From Mouse to Man

The development of the adaptive immune system has been studied in the mouse primarily because it is easier to access fetal tissues and because there exists a rich array of probes for analysis of various components of the immune system. While much has been learned from this exercise, it is also clear that different species show substantial temporal variation in the development of the immune system during early life. In mice, for instance, mature alpha/beta T cells first appear in the periphery during the final stages of fetal gestation and only increase in number after birth (Friedberg and Weissman, 1974); in humans, on the other hand, the first mature alpha/beta T cells are seen in peripheral tissues at 10-12 gestational weeks (g.w.) and are circulating in significant numbers by the end of the second trimester (Ceppellini et al., 1971; Haynes et al., 1988; Hayward and Ezer, 1974; Kay et al., 1970). Although the functional implications of these differences remain unclear, it is likely that there are significant biological consequences associated with the relatively early development of the peripheral adaptive immune system in humans, for example, with respect to the development of peripheral tolerance as well as to the response to antigens that might cross the placenta from the mother (e.g., cells bearing noninherited maternal alloantigens, infectious agents, food antigens, and the like). Here, we will review studies of immune system ontogeny in the mouse and in humans, and then focus on the possible functional roles of fetal T cell populations during development and later in life in humans.