MECHANISMS OF RECOVERY FROM EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS- T-CELL DELETION AND IMMUNE DEVIATION IN MYELIN BASIC-PROTEIN T-CELLRECEPTOR TRANSGENIC MICE

Experimental autoimmune encephalomyelitis (EAE) is a Th1-type cell-med iated autoimmune disease directed against central nervous system (CNS) myelin antigens such as myelin basic protein (MBP). EAE is usually ch aracterized by spontaneous remission of clinical disease and immune pa thology despite the persistence of self myelin antigens in the central nervous system. Following induction of an acute episode of EAE, spont aneous remission also occurs in MBP T cell receptor (TCR) transgenic m ice even though most T cells express a TCR specific for MBP. To invest igate the mechanisms of recovery associated with EAE, we examined the behavior of MBP-specific T cells in the MBP TCR transgenic mouse model during disease progression and recovery. We found that recovery from EAE was associated with three major immunologic changes. (1) deletion of encephalitogenic T cells in the brain; (2) deviation of MBP-specifi c transgenic (Tg(+))T cells both in the periphery and in the central n ervous system from IFN-gamma secreting Th1 type cells to cells that se crete IL-4. IL-10, and TGF-beta, and (3) deletion of Te+ T cells in th e thymus through apoptosis. Thus spontaneous recovery from a classic T h1 type organ specific autoimmune disease is associated with two mecha nisms of immune tolerance, deletion of autoreactive cells and immune d eviation of autoreactive cells to a non-pathogenic phenotype. (C) 1998 Published by Elsevier Science B.V.