Tolerance mechanism in experimental ovarian and gastric autoimmune diseases.
Neonatal splenocytes, neonatal thymocytes, or phenotypically mature adult thymocytes, transferred from normal BALB/c mice to syngeneic athymic nu/nu (or SCID) mice, led to autoimmune oophoritis and autoimmune gastritis, with corresponding serum autoantibodies, in the recipients. The overall disease incidence was 73%; the pathology ranged from mild to severe, with complete loss of ovarian follicles and gastric parietal cells. CD4+ neonatal spleen cells and CD4+ CD8- adult thymocytes were required for autoimmune disease induction. Adult spleen cells did not elicit disease, but they prevented disease when co-transferred with neonatal spleen cells. However, in confirmation of an earlier report by Sakaguchi et al., (J. Exp. Med. 161:72, 1985), a subset of adult splenic T cells expressing a low level of CD5 molecules elicited similar autoimmune diseases. Thus, self-reactive T cells responsible for autoimmune disease of the stomach and ovary are not effectively deleted in the thymus, and they exist in the peripheral lymphoid organs of normal mice. We conclude that the functional expression of the self-reactive T cells is ontogenetically regulated; whereas T cells in the neonatal mice readily elicited autoimmune diseases in nu/nu recipients, regulatory cells may render self-reactive T cells in the normal adults unresponsive.
Smith
H
H
Department of Pathology and Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Lou
Y H
YH
Lacy
P
P
Tung
K S
KS
D000818:Animals; D000831:Animals, Newborn / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018956:CD5 Antigens; D005260:Female; D005756:Gastritis / Q000276:immunology*; D007108:Immune Tolerance; D007116:Immunization, Passive; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D009869:Oophoritis / Q000276:immunology*; D010053:Ovary / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D013270:Stomach / Q000276:immunology
D015703:Antigens, CD; D001323:Autoantibodies; D018956:CD5 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta