Effect of timing of intravenous administration of myelin basic protein on the induction of tolerance in experimental allergic encephalomyelitis

Immunological tolerance and suppression of clinical and histological experi mental allergic encaphalomyelitis (EAE) can be induced by the intravenous ( i.v.) administration of myelin basic protein (MBP). In this report we have characterized the effect of the time of Iv. administration of MBP on the co urse of EAE in Lewis rots. Rots were treated with the i.v. administration o f one or two 500 mu g doses of MBP either before or after active immunizati on. Results indicated that iv administration of MBP in rots before active i mmunization with MBP/CFA (naive rats) was most effective when given 14 days before naive immunization, but treatment of rats actively immunized with M BP (immunized rats) was most effective at the onset of disease. Treatment a t other times was less effective. The i.v. administration of the peptide MB P 68-88 (p68-88) containing the dominant encephalitogenic epitope could als o suppress MBP-induced EAE in a dose dependent manner Intravenous administr ation of two injections of p68-88 to naive rats on days 10 and 3 before, or on days 0 and 7 after, active immunization with MBP suppressed the develop ment of EAE in a dose dependent manner. Treatment of rots with iv. MBP afte r, but not before, the transfer of MBP-reactive EAE effector cells suppress ed the development of EAE in the recipient rots. Transfer of lymphoid cells from tolerized naive rats failed to protect recipient rots against develop ment of active or passive EAE These results indicate the importance of timi ng and dose of the antigen on the induction of tolerance and suggests diffe rent mechanisms of tolerance induction by intravenous MBP in immunized and naive rats. They also emphasize the importance of timing in designing effic ient treatment strategies when iv. tolerance is contemplated in EAE and pos sibly multiple sclerosis.