Differential control of neonatal tolerance by antigen dose versus extendedexposure and adjuvant

Ig-PLP1, an immunoglobulin (Ig) chimera carrying the encephalitogenic prote olipid protein (PLP) sequence 139-151 (PLP1), induces neonatal tolerance in mice and confers resistance to experimental allergic encephalomyelitis (EA E) without the need for incomplete Freund's adjuvant (IFA). The mechanism u nderlying such tolerance involves organ-specific T cell regulation characte rized by lymph node deviation and an unusual IFN gamma-dependent splenic an ergy. This form of T cell modulation may prove useful for prevention of aut oimmunity. However, since the neonatal period is susceptible to regulation, further investigations are necessary to define parameters required to esta blish regimens suitable for optimal protection against disease. Therefore, studies were carried out to investigate the effect that IFA, the dose of Ig -PLP1, and the number of Ig-PLP1 injections might have on Ig-PLP1-mediated neonatal tolerance and protection against disease. Herein it is reported th at as little as 1 mu g of Ig-PLP1 supported IFN gamma-dependent splenic ane rgy but lymph node deviation and protection against disease strengthened as the dose of tolerogen increased. However, when a two-injection regimen was applied, resistance to disease was observed but the mechanism manifested p roliferative and cytokine unresponsiveness in both lymphoid organs. Further more, the use of IFA along with Ig-PLP1 yielded a suppressive mechanism sim ilar to that of the two-injection regimen. Therefore, the dose of Ig-PLP1 d isplays a quantitative influence, while the number of injections of Ig-PLP1 and the presence of IFA rather drive qualitative influences on such tolera nce. (C) 2000 Academic Press.