T cell reactivity to acetylcholine receptor in rats orally tolerized against experimental autoimmune myasthenia gravis.

Myasthenia gravis and its animal model experimental autoimmune myasthenia gravis (EAMG) represent T cell-dependent autoimmune diseases mediated by antibodies against the nicotinic acetylcholine receptor (AChR) of the neuromuscular junction. Oral administration of Torpedo AChR to Lewis rats prior to immunization with the myasthenogenic Torpedo AChR and complete Freund's adjuvant results in the prevention of clinical EAMG, and the suppression of AChR-specific B cell responses. To examine the influence of oral tolerance to EAMG on AChR-reactive T cells, we determined and enumerated such cells in the popliteal, inguinal, and mesenteric lymph nodes, spleen, and thymus by a T cell immunospot assay that is based on the secretion of interferon-gamma (IFN-gamma) by antigen-reactive T cells. A diminution of such cells was detected in popliteal, inguinal, and mesenteric lymph nodes of rats orally tolerized to EAMG compared to unfed or vehicle-fed animals. We conclude that oral administration of AChR, in addition to preventing clinical signs of EAMG and suppressing AChR-specific B cell responses, also counteracts the development of AChR-reactive IFN-gamma-secreting cells in certain lymphoid organs.