Role of late complement components in experimental autoimmune thyroiditis.
Availability of a line of rabbits deficient in the sixth complement component (C6-D) made it possible to evaluate the role of the terminal complement complex (TCC) in the development of experimental autoimmune thyroiditis (EAT) of the rabbit. Immunization with saline extract of homologous thyroid, known to be composed predominantly of thyroglobulin, led in normocomplementemic (NC) rabbits to severe thyroiditis, with cellular infiltrates occupying 50-95% of the thyroid, and to minimal or moderate thyroiditis, with 1-35% of thyroids infiltrated in C6-D rabbits. Cellular infiltrates consisted predominantly of mononuclear cells with appreciable numbers of granulocytes. Destruction of thyroid follicles was extensive and diffuse in NC rabbits, but it was only minimal and focal in C6-D rabbits. Immunohistology revealed in both groups of rabbits deposits of IgG and C3 along follicular basal laminae. In addition, NC rabbits showed deposition of C6 and MAC in thyroid follicles. These results suggested that TCC is necessary for the development of fully expressed, severe EAT; simultaneously, however, they showed that a significantly reduced EAT can develop without TCC. Administration of NC but not of C6-D rabbit serum to C6-D rabbits resulted in a significant increase in the severity of EAT. It was also shown that C6-D rabbits have "normal" T-cell activity, since they developed experimental autoallergic encephalomyelitis as readily as NC rabbits. Therefore, it is likely that development of EAT is indeed impaired by the C6 deficiency in rabbits. The requirement for TCC observed in this study may be relevant to the understanding of the pathogenesis of Hashimoto's thyroiditis, in which thyroid tissue was recently shown to contain TCC deposits.
Inoue
K
K
Department of Microbiology, State University of New York, Buffalo 14214.
Niesen
N
N
Biesecker
G
G
Milgrom
F
F
Albini
B
B
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D003183:Complement C6 / Q000172:deficiency*; D003165:Complement System Proteins / Q000502:physiology*; D005260:Female; D007074:Immunoglobulin G / Q000032:analysis; D007958:Leukocyte Count; D008297:Male; D009000:Monocytes / Q000166:cytology; D011817:Rabbits; D013601:T-Lymphocytes / Q000166:cytology; D013961:Thyroid Gland / Q000737:chemistry / Q000166:cytology; D013967:Thyroiditis, Autoimmune / Q000276:immunology*
D003183:Complement C6; D007074:Immunoglobulin G; D003165:Complement System Proteins