Suppression of experimentally induced autoimmune encephalomyelitis by cytolytic T–T cell interactions

Abstract

Down-regulatory phenomena have been described in several experimental models of tissue-specific, T-cell-mediated autoimmunity. For example, resistance to active induction of experimental autoimmune encephalomyelitis (EAE) can be induced by pretreating animals with non-pathogenic inocula of autoantigen¹ or effector cells^2,3. Moreover, animals that have recovered from one EAE episode are resistant to subsequent induction of EAE^4–6. In some models, resistance to EAE has been transferred with immune cells to naive recipients^7–12. These experiments, which were based on transfers of unseparated immune cell populations, are difficult to intepret. Immune suppression circuits are known to be complex and involve various distinct cellular subsets¹³. To further complicate the issue, resistance to EAE can be transferred not only by suppressor cells, but also by encephalitogenic effector cells injected in 'subclinical' doses^2,12. We describe now the isolation of homogenous T lymphocyte lines from the spleens of Lewis rats that had recovered from T-cell-mediated EAE (tEAE) caused by the MBP-specific T cell line SI. These spleen-derived T line cells express the CDS phenotype and specifically respond to determinants on the inducing SI line, but not to the autoantigen MBP. Furthermore, the anti-Si cells selectively lyse the encephalitogenic SI T line in vitro and efficiently neutralize their encephalitogenic capacity in vivo.