Resistance to experimental autoimmune thyroiditis: L3T4+ cells as mediators of both thyroglobulin-activated and TSH-induced suppression.
Mechanisms suppressive to induction of murine experimental autoimmune thyroiditis (EAT) can be activated by pretreatment with tolerogenic doses of mouse thyroglobulin (MTg) or prior TSH infusion to raise circulatory MTg levels. MTg-activated suppressor T cells (Ts), shown earlier to be Thy-1+ and probably I-J+, were further characterized by in vivo administration of paired rat monoclonal antibodies to distinct epitopes on the L3T4 or Lyt-2 molecule, either on the day of, or subsequent to, initiation of the tolerogenic regimes. The cells required at the time of MTg pretreatment were L3T4+, Lyt-2- and low anti-L3T4 doses had no effect on their activation. The cells that mediated the strong MTg-induced resistance following pretreatment were also L3T4+; their suppressor function could only be abrogated by depletion of L3T4+, but not Lyt-2+, cells. Injection of cyclophosphamide (20-100 mg/kg) either prior to EAT induction or after Ts activation did not affect the severity of disease. Similarly, the suppressor state evoked by TSH infusion could only be abrogated by anti-L3T4 treatment. These findings indicate that both MTg-activated and TSH-induced suppression are mediated by L3T4+ cells. We hypothesize that MTg-specific Ts are present in normal, EAT-susceptible mice in low numbers to contribute to the maintenance of self-tolerance and that they are stimulated by increased levels of circulatory MTg to expand/differentiate and mediate the marked resistance to EAT induction.
Kong
Y M
YM
Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan 48201.
Giraldo
A A
AA
Waldmann
H
H
Cobbold
S P
SP
Fuller
B E
BE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D000950:Antigens, Ly / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003520:Cyclophosphamide / Q000494:pharmacology; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013954:Thyroglobulin / Q000276:immunology*; D013967:Thyroiditis, Autoimmune / Q000276:immunology*; D013972:Thyrotropin / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D003520:Cyclophosphamide; D013972:Thyrotropin; D013954:Thyroglobulin