MYELIN ANTIGEN-COUPLED SPLENOCYTES SUPPRESS EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS IN LEWIS RATS THROUGH A PARTIALLY REVERSIBLE ANERGY MECHANISM

Mechanisms of adult tolerance induced by injecting myelin Ag/ECDI (eth yl carbodiimide)-coupled splenocytes (Ag-SPL) were evaluated in Lewis rat experimental autoimmune encephalomyelitis (EAE). Rats could be tol erized against the major encephalitogenic epitope of guinea pig basic protein (Cp-BP), residues 72-89, using either S72-89-SPL or crude spin al cord homogenate (SCH)-SPL. In contrast to lymph node responses that were not affected significantly, the proliferation responses of blood T cells were markedly inhibited at the peak of EAE and during the rec overy period to both Gp-BP and S72-89, but not to purified protein der ivative (PPD), demonstrating Ag-specific tolerance. Tolerance inductio n reduced the number of infiltrating spinal cord (SC) cells, especiall y recruited CD45RC(+) cells, as well as SC proliferation responses to S72-89 throughout the course of EAE. In contrast, SC response tb PPD w as increased at onset of EAE,.but later during recovery the PPD respon se was also decreased compared with control rats. Tolerance induced by S72-89-SPL in blood and SC T cells could be reversed by incubation in IL-2, in accordance with an anergy model. BP-specific T cells preincu bated in vitro with Cp-BP-SPL were rendered unresponsive to Gp-BP or S 72-89, compared with the same T cells preincubated with histone (Hist) -SPL that remained Ag responsive. Consistent with an anergy model, pre incubation with EP-SPL + IL-2 partially prevented tolerance induction to BP. T cells tolerized in vitro to BP-SPL induced milder EAE with de layed onset compared with control-tolerized T cells that produced leth al disease. These results demonstrate the efficacy of myelin Ag-couple d SPL in preventing EAE by selective tolerization of encephalitogenic T cells through a partially reversible anergy-induction mechanism.