Macrophage and lymphocyte functions are down-regulated in newborn rabbits

We have developed an animal model for congenital syphilis. Treponema pallidum is injected intravenously into pregnant rabbits and fetuses are infected in utero. As a prelude to characterizing the immunologic consequences of fetal infection, it was necessary to expand on the baseline information about newborn rabbit immune capabilities. Studies were undertaken to determine splenic macrophage and T lymphocyte functions with emphasis on newer immunologic parameters. Newborns aged 2 weeks were compared to adults. Macrophage capabilities in newborn rabbits differed from those of their adult counterparts. These cells produced similar basal levels of interleukin 1 (IL-1) but failed to respond to the IL-1 stimulants of lipopolysaccharide (LPS) or T. pallidum. Macrophages also exhibited diminished levels of la expression and increased levels of prostaglandin E2 (PGE2) secretion. T lymphocyte functions were altered in newborn spleen preparations. Following concanavalin A (Con A) stimulation, interferon gamma production was half that of adults; in direct contrast, IL-2 production was twice that of adults. Con A-induced lymphocyte proliferation was markedly decreased in newborn preparations. This diminished response resulted from down-regulation rather than immaturity. When newborn splenic cells were stimulated with Con A in the presence of indomethacin, anti-transforming growth factor (anti-TGF), or exogenous IL-1/IL-2, better proliferation resulted. PGE2, which is well established as a down-regulator of newborn immune functions in human and mouse systems, also appears to play a role in suppressing newborn rabbit functions. TGF is a potent suppressor of a number of adult immunologic reactions. This is the first documentation of the potential role of this factor in down-regulating newborn immune capabilities. These findings provide a framework for future investigations of our congenital syphilis model.