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
Ben-Nun, A.; Cohen, I.R.
Journal of Immunology 128(3): 1450-1457
1982
ISSN/ISBN: 0022-1767 PMID: 6173439 Document Number: 186032
Experimental autoimmune encephalomyelitis (EAE) 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 2nd bout of EAE. Mechanisms involved in spontaneous recovery and acquired refractoriness to EAE were elucidated by investigating several variables as a function of the clinical stage of disease. The differential proliferative responses of T lymphocytes to specific antigenic determinants of BP were studied; the presence of suppressor cells was detected by their influence on antigen-specific T lymphocyte lines in vitro. Suppressed effector T lymphocytes were isolated by growing them as cell lines. 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. 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. Thymic suppressor cells appeared to recognize specifically T cells with anti-BP receptors. 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. 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-tolerance to BP and acquired resistance to EAE were regulated by reversible suppression of specific effector T lymphocytes reactive against critical self-antigenic determinants.