Regulation of autoreactive T cell responses by neonatal exposure to a self-peptide Ig-chimera

Prior investigations from this laboratory reported that exposure of the neonatal immune system to an immunoglobulin (Ig) chimera carrying a proteolipid protein (PLP) peptide drives the adult response to a challenge with the PLP peptide towards T cell deviation in the lymph node and an IFN-y-dependent T cell energy in the spleen. In addition, such exposure protects against experimental allergic encephalomyelitis (EAE). Herein, we wished to determine whether such a biased response is intrinsic to the PLP peptide or emanates from the delivery by Ig, thus allowing a similar outcome to ensue with other myelin peptides. Accordingly, the amino acid sequence 87-99 of myelin basic protein (MBP) was expressed on the same Ig backbone, and the resulting Ig-MBP chimera was tested for induction of neonatal immunity and protection against EAE involving diverse T cell specificities. The results revealed Th2 deviated T cell responses in both lymphoid organs, and the animals resisted induction of EAE. 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 encephalitogenic determinants and promoting protection against autoimmunity involving diverse T cell specificities. Thus, exposure of the neonatal immune system to antigenic peptides in the context of a self-Ig molecule fosters the development of a broad-spectrum protective immunity emanating from organ specific regulatory functions.