'Split tolerance' induction by intrathymic injection of acetylcholine receptor in a rat model of autoimmune myasthenia gravis; implications for the design of specific immunotherapies.
Experimental autoimmune myasthenia gravis (EAMG) in the Lewis rat, induced by a single injection of acetylcholine receptor (AChR) protein, is a model used to study human myasthenia gravis (MG). The production of anti-AChR antibodies in the animal model and human MG is T cell-dependent, and AChR-specific T cells have been considered as a potential target for specific immunotherapy. Intrathymic injection of antigens induces antigen-specific tolerance in several T cell-mediated autoimmune models. We examined the effect of intrathymic injection of AChR on T cell responses and the production of antibodies to AChR in EAMG rats. Primed lymph node cells from rats receiving intrathymic injection of AChR exhibited reduced proliferation to AChR with marked suppression of interferon-gamma (IFN-gamma) secretion in the antigen-stimulated culture, compared with those of rats injected with PBS. However, neither anti-Narke AChR nor anti-rat AChR antibody production was suppressed or enhanced in intrathymically AChR-injected animals compared with that of animals injected intrathymically with PBS or perithymically with AChR. This 'split tolerance' may be attributable to the suppression of type-1 T helper cells (Th1). Our results suggest that the suppression of Th1 function alone may not be sufficient for the prevention of antibody-mediated autoimmune diseases.
Ohtsuru
I
I
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Matsuo
H
H
Fukudome
T
T
Suenaga
A
A
Tsujihata
M
M
Nagataki
S
S
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007114:Immunization; D007167:Immunotherapy; D007371:Interferon-gamma / Q000096:biosynthesis; D009157:Myasthenia Gravis / Q000276:immunology* / Q000628:therapy; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology*
D001323:Autoantibodies; D011950:Receptors, Cholinergic; D007371:Interferon-gamma