SUPPRESSION OF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS BY ORAL-ADMINISTRATION OF MYELIN BASIC-PROTEIN .6. SUPPRESSION OF ADOPTIVELY TRANSFERRED DISEASE AND DIFFERENTIAL-EFFECTS OF ORAL VS INTRAVENOUS TOLERIZATION

Antigen-driven tolerance is an effective method of suppressing cell-me diated immune responses. We have previously shown that oral administra tion of myelin basic protein (MBP) suppresses experimental autoimmune encephalomyelitis (EAE) when it is actively induced by MBP emulsified in complete Freund's adjuvant. In order to further study antigen-drive n tolerance in this model, we investigated the effect of oral toleriza tion on adoptively transferred EAE and compared oral tolerance to intr avenously (i.v.) administered MBP in both actively induced EAE and ado ptively transferred EAE. Although orally tolerized animals were not pr otected from adoptively transferred EAE, spleen cells from orally tole rized animals suppressed adoptively transferred EAE when co-transferre d with encephalitogenic cells or when injected into recipient animals at a different site at the time encephalitogenic cells were transferre d. This suppression was mediated by CD8+ T cells, correlated with supp ression of DTH responses to MBP, and was associated with decreased inf lammation in the spinal cord. Unlike oral tolerization, spleen cells f rom i.v. tolerized animals did not suppress adoptively transferred EAE when co-transferred with encephalitogenic cells although i.v. toleriz ed animals were protected from adoptively transferred EAE. MBP peptide s were then utilized to further characterize differences between i.v. and oral tolerization in the actively induced disease model. Both oral ly and intravenously administered MBP suppressed actively induced EAE. However, EAE was only suppressed by prior i.v. tolerization with the encephalitogenic MBP peptide 71-90, but not with the non-encephalitoge nic peptide 21-40, whereas prior tolerization with 21-40 did suppress actively induced EAE when administered orally. These results suggest a different mechanism of tolerance is initiated by oral vs. intravenous administered antigen. Specifically, oral tolerization suppresses prim arily by the generation of active suppression whereas the dominant mec hanism of suppression' associated with i.v. tolerization appears most consistent with the elicitation of clonal anergy.