Induction of autoimmunity with dendritic cells: studies on thyroiditis in mice.

The initiation and maintenance of thyroid autoimmunity by professional antigen-presenting cells were assessed by observing thyroiditis and induction of IgG antibodies to thyroglobulin (Tg). Dendritic cells (DC) were purified from spleens of CBA mice and T cells removed with anti-Thy 1 and complement. Some DC were pulsed with 25-500 micrograms/ml of mouse Tg in vitro and normal syngeneic mice received injections of 10(5) cells intravenously. In untreated animals only 1 thyroid out of 40 showed a lymphocyte infiltrate and antibody to Tg was rarely seen. In animals receiving normal DC without Tg, lymphocyte infiltration was seen 2-6 weeks later in 5 out of 33 thyroids and some animals produced low levels of antibody to thyroglobulin (8 of 33 animals). DC pulsed with 500 micrograms Tg/ml in vitro caused thyroid infiltration in 6 out of 15 animals but did not increase the incidence of anti-Tg antibodies. Lower doses had no effect. When 10(5) DC were given from animals with experimental allergic thyroiditis (EAT, induced with Tg in complete Freund's adjuvant, CFA) more than half of the recipient animals showed thyroiditis (8 out of 15) and autoantibody production (12 of 15 animals). DC may therefore play a role in the initiation and maintenance of autoimmunity by providing a stimulus for antigen-specific T cells.