ACQUIRED TOLERANCE TO EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS BY INTRATHYMIC INJECTION OF MYELIN BASIC-PROTEIN OR ITS MAJOR ENCEPHALITOGENIC PEPTIDE

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory dis ease of the central nervous system that can be induced in a number of species by immunization with myelin basic protein (MBP) in adjuvant, a nd serves as an experimental model for the study of multiple sclerosis . The role of the thymus in acquired tolerance in autoimmune models ha s not been thoroughly investigated. In this study, we examined the eff ects of intrathymic injection of MBP or its major encephalitogenic pep tide on the course of EAE in Lewis rats. A single intrathymic injectio n of MBP 48 h pre- but not postimmunization protects animals from acti vely induced EAE. An intact MBP-primed thymus was required up to 10 d postimmunization, as thymectomy on days 1, 2, and 7 postimmunization a brogated the protective effect, whereas thymectomy on day 10 did not. The proliferative response of primed lymphocytes was significantly red uced in animals that were intrathymically injected with MBP. Protectio n against clinical EAE was induced by thymic injection of the major en cephalitogenic region (residues 71-90) but not a nonencephalitogenic ( 21-40) MBP epitope. Immunohistologic examination of the brain from rat s intrathymically injected with encephalitogenic peptide showed marked ly reduced cellular infiltrate and virtual absence of activation and i nflammatory cytokines as compared with rats intrathymically injected w ith the nonencephalitogenic peptide. These results indicate that the t hymus may play an active role in acquired systemic immunologic toleran ce in T cell-mediated experimental autoimmune diseases. This effect ma y be mediated by a process of clonal inactivation of autoreactive T ce ll clones circulating through the thymus.