Spontaneous remission and acquired resistance to autoimmune encephalomyelitis (EAE) are associated with suppression of T cell reactivity: suppressed EAE effector T cells recovered as T cell lines.

Experimental autoimmune encephalomyelitis (EAE) is a disease that can be induced in Lewis rats by inoculating them with myelin basic protein (BP) emulsified in complete Freund’s adjuvant. Rats spontaneously recover from EAE and subsequently become refractory to attempts to induce a second bout of EAE. Mechanisms involved in spontaneous recovery and acquired refractoriness to EAE were elucidated by investigating a number of variables as a function of the clinical stage of disease. We studied the differential proliferative responses of T lymphocytes to specific antigenic determinants of BP, detected the presence of suppressor cells by their influence on antigen-specific T lymphocyte lines in vitro, and isolated suppressed effector T lymphocytes by growing them as cell lines. The following results were obtained: 1) Onset of EAE and spontaneous recovery correlated with the rise and fall of T lymphocyte responses in the draining lymph nodes to specific encephalitogenic determinants of BP. The responses to other determinants of BP were not related to the clinical stage of EAE. 2) Depression of this T lymphocyte response to critical antigenic determinants was associated with the appearance of immunospecific suppressor cells, most prominent in the spleen and thymus. 3) Thymic suppressor cells appeared to recognize specifically T cells with anti-BP receptors. 4) Suppressed EAE effector T lymphocytes were rescued from the thymus, spleen, and lymph nodes of rats recovered from and refractory to EAE by selecting and propagating these cells in vitro as lines. Upon i.v. inoculation, cells of these rescued T lymphocyte lines produced EAE in naive recipients. 5) Suppressor cells and suppressed EAE effector T lymphocytes were also detected in rats that had been injected with nonencephalitogenic BP in incomplete Freund’s adjuvant. Thus, spontaneous restoration of self-toleranee to BP and acquired resistance to EAE were regulated by reversible suppression of specific effector T lymphocytes reactive against critical self-antigenic determinants.