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 proteolipid
protein (PLP)
peptide on Ig boosts the neonatal immune system to develop responses upon challenge with the PLP
peptide later. Accordingly, mice given 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 usual Th1
cytokines. However, the spleen was unresponsive unless
IL-12 was provided. Herein, we wished to determine whether such a neonatal response is intrinsic to the PLP
peptide or could develop with an unrelated myelin
peptide as well as whether the T cell deviation is able to confer resistance to autoimmunity involving diverse T cell specificities. Accordingly, the amino 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 allergic encephalomyelitis. Surprisingly, the results indicated that immunity developed 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 responses to unrelated
epitopes and promoted protection against
experimental allergic encephalomyelitis involving diverse T cell specificities. Thus, neonatal exposure to Ag can prime responses in various organs and sustain regulatory functions effective against diverse autoreactive T cells.