The generation of th memory in neonates versus adults: Prolonged primary Th2 effector function and impaired development of Th1 memory effector function in murine neonates

Immunization during the neonatal period often results in Th2-biased seconda ry responses. To understand the regulation of this phenomenon, we have exam ined all phases of Th development, from the generation of primary effecters to the duration of the primary effector stage to the production of memory effector function. First, we had previously reported that although primary responses in the neonatal lymph nodes are mature, mixed Th1/Th2-like, prima ry responses in the spleens of the same animals are exclusively Th2-like. T o determine whether Th2-dominant secondary responses are due to the Th2-pol arized primary function in the spleen, neonates were splenectomized before immunization. Even in the absence of primary neonatal splenic responses, th e secondary responses of neonates were Th2 dominant. Thus, the overwhelming ly Th2 primary responses in the neonatal spleen are not required to generat e Th2-dominant memory in the lymph nodes. Second, we have compared the kine tics of the primary response phase in neonates and adults. In adults, Ag-sp ecific Th2 function disappeared rapidly from both the lymph nodes and splee n, In contrast, primary Th2 function persisted out to 5 wk in both neonatal organs. Third, the generation of Th memory responses was examined in anima ls initially immunized as neonates and in adults, These experiments demonst rated that neonates are selectively impaired in the development of Th1 memo ry effector function. Together, these results indicate that neonates are bi ased to Th2 function at all phases of an immune response.