PROTECTION FROM EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS (EAE) - NON-DEPLETING ANTI-CD4 MAB TREATMENT INDUCES PERIPHERAL T-CELL TOLERANCE TO MBP IN PL J MICE/

Following pre-treatment with a non-depleting anti-CD4 mAb (H129.19) th at produces long-lasting receptor Saturation, PL/J mice were fully pro tected from experimental auto-immune encephalomyelitis (EAE) induced b y injection of myelin basic protein (MBP). These mice did not develop EAE following MBP re-challenge 5-10 weeks later when the CD4(+) cells were no longer coated by the mAb and their lymph node cells were speci fically unresponsive to MBP stimulation in vitro. Moreover, superantig en staphylococcal enterotoxin B (SEB) inoculation, which re-induces EA E in MBP immunized mice, failed to activate encephalitogenic T-cells i n anti-CD4 + MBP treated mice, even after MBP re-challenge, indicating that tolerance in the peripheral T-cell compartment was achieved. How ever, MBP re-challenge 16 weeks later, but not SEB, produced an acute episode of EAE in these mice, while it failed to induce disease in a p arallel group of adult thymectomized mice. These results indicate that no memory of the first priming exists at this time and that new MBP-s pecific T-cell precursors are peripheralized and produce EAE after MBP recognition.