Neonatal exposure to antigen primes the immune system to develop responsesin various lymphoid organs and promotes bystander regulation of diverse T cell specificities

Neonatal exposure to Ag has always been considered suppressive for immunity . Recent investigations, however, indicated that the neonatal immune system could be guided to develop immunity. For instance, delivery of a proteolip id protein (PLP) peptide on Ig boosts the neonatal immune system to develop responses upon challenge with the PLP peptide later. Accordingly, mice giv en Ig-PLP at birth and challenged with the PLP peptide as adults developed proliferative T cells in the lymph node that produced IL-4 instead of the u sual Th1 cytokines. However, the spleen was unresponsive unless IL-12 was p rovided. Herein, we wished to determine whether such a neonatal response Is intrinsic to the PLP peptide or could develop with an unrelated myelin pep tide as well as whether the T cell deviation is able to confer resistance t o autoimmunity involving diverse T cell specificities. Accordingly, the ami no acid sequence 87-99 of myelin basic protein was expressed on the same Ig backbone, and the resulting Ig-myelin basic protein chimera was tested for induction of neonatal immunity and protection against experimental allergi c encephalomyelitis. Surprisingly, the results indicated that immunity deve loped in the lymph node and spleen, with deviation of T cells occurring in both organs. More striking, the splenic T cells produced IL-10 in addition to IL-4, providing an environment that facilitated bystander deviation of r esponses to unrelated epitopes and promoted protection against experimental allergic encephalomyelitis involving diverse T cell specificities. Thus, n eonatal exposure to Ag can prime responses in various organs and sustain re gulatory functions effective against diverse autoreactive T cells.