Inhibition of murine relapsing experimental autoimmune encephalomyelitis by immune tolerance to proteolipid protein and its encephalitogenic peptides

Tolerization of SJL/J mice with splenocytes coupled with proteolipid protein (PLP), the major protein component of central nervous system myelin, resulted in dramatic inhibition of relapsing experimental autoimmune encephalomyelitis (R-EAE) induced by mouse spinal cord homogenate (MSCH). Mice tolerized with splenocytes coupled with MSCH (a complex mixture of neuroantigens) or with purified PLP, but not purified myelin basic protein, were resistant to the development of clinical and histologic R-EAE. In addition, mice rendered tolerant to an encephalitogenic peptide of PLP were significantly protected, whereas mice tolerized to a nonencephalitogenic peptide of PLP were highly susceptible, to the induction of MSCH-induced R-EAE. Thus, immune responses directed against encephalitogenic regions of PLP appear to play a major role in the development of R-EAE induced by MSCH in SJL/J mice. These results also indicate that determinant-specific immune tolerance is a feasible approach to the regulation of a disease that involves autoimmune responses to a variety of Ag.