TREATMENT OF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS BY FEEDING MYELIN BASIC-PROTEIN CONJUGATED TO CHOLERA-TOXIN-B SUBUNIT

Oral administration of autoantigens can prevent and partially suppress autoimmune diseases in a number of experimental models, Depending on the dose of antigen fed, this approach appears to involve distinct yet reversible and short-lasting mechanisms (anergy/deletion and suppress ion) and usually requires repeated feeding of large (suppression) to m assive (anergy/deletion) amounts of autoantigens to be effective, Most importantly, this approach is relatively less effective in animals al ready systemically sensitized to the fed antigen, such as in animals a lready harboring autoreactive T cells and, thus, presumably also in hu mans suffering from an autoimmune disorder, We have previously shown t hat feeding a single dose of minute amounts of antigens conjugated to cholera toxin B subunit (CTB) can effectively suppress delayed-type hy persensitivity reactions in systemically immune animals. We now report that feeding small amounts of myelin basic protein (MBP) conjugated t o CTB either before or after disease induction protected rats from exp erimental autoimmune encephalomyelitis, Such treatment was as effectiv e in suppressing interleukin 2 production and proliferative responses of lymph node cells to MBP as treatment involving repeated feeding wit h much larger (50- to 100-fold) doses of free MBP. Different from the latter treatment, which led to decreased production of interferon-gamm a in lymph nodes, low-dose oral CTB-MBP treatment was associated with increased interferon-gamma production, Most importantly, low-dose oral CTB-MBP treatment greatly reduced the level of leukocyte infiltration into spinal cord tissue compared with treatment with repeated feeding of large doses of MBP, These results suggest that the protection from experimental autoimmune encephalomyelitis achieved by feeding CTB con jugated myelin autoantigen involves immunomodulating mechanisms that a re distinct from those implicated by conventional protocols of oral to lerance induction.