Effects of anti-I-A and anti-I-E monoclonal antibodies on the induction and expression of experimental autoimmune thyroiditis in mice.
Susceptibility to experimental autoimmune thyroiditis (EAT) in mice is linked to the I-A subregion of the major histocompatibility complex (MHC). The present study was undertaken to assess the effectiveness of anti-I-Ak monoclonal antibody (MAb) 10-2.16 in preventing or arresting the development of EAT. Spleen cells from CBA/J or (CBA/J x Balb/c) F1 mice given 10-2.16 prior to sensitization with mouse thyroglobulin (MTg) and adjuvant could not transfer EAT to normal recipients, and cells from these mice did not proliferate in vitro to MTg. Donor CBA/J mice given 10-2.16 before immunization and recipients of cells from such mice produced little MTg-specific IgG1 or IgG2b antibody but did produce nearly as much IgG2a as controls. The effects of in vivo treatment with 10-2.16 appear to be due to elimination of Ia + cells rather than to modulation of Ia or induction of suppressor T cells. When 10-2.16 was added to in vitro cultures it also prevented the proliferation and activation of sensitized CBA/J or F1 effector cell precursors. Other mAb specific for MHC class II gene products, but not associated with disease susceptibility, expressed by CBA/J (I-Ek) or F1 (I-Ad) mice (14-4-4S or MK-D6 respectively), also prevented in vivo sensitization, but did not block in vitro activation. Anti-I-Ak was also effective in preventing EAT if multiple injections of mAb were given to recipients of sensitized EAT effector cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Stull
S J
SJ
Department of Microbiology, University of Missouri, Columbia 65212.
Kyriakos
M
M
Sharp
G C
GC
Bickel
J T
JT
Braley-Mullen
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D007074:Immunoglobulin G / Q000096:biosynthesis; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013954:Thyroglobulin / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000209:etiology* / Q000517:prevention & control
D000911:Antibodies, Monoclonal; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D007074:Immunoglobulin G; D013954:Thyroglobulin