PROSPECTIVE-STUDY OF T-CELL RECEPTOR UTILIZATION FOLLOWING THE INDUCTION OF MURINE THYROIDITIS

Murine experimental autoimmune thyroiditis (EAT) is a well established model of autoimmune disease initiated by immunization with thyroglobu lin. We have previously analyzed the T cell receptor (TcR) V gene fami lies used by the intrathyroidal lymphocytic infiltrate in CBA/J mice w ith well established thyroiditis EAT and have implicated T cells expre ssing the mTcR V(beta)13 gene family. We have now proceeded to examine the time course of mTcR V gene family use following immunization with mTg. We used a radiolabelled RT-PCR technique with oligonucleotides d etecting 17 mouse TcR V-beta gene families to examine the heterogeneit y of the amplified V-D-J (CDR3) fragments. As previously, the TcR V(be ta)13 amplifications showed the expression of two similar homogeneous CDR3 sizes consistent with two clonally expanded T cell populations. H owever, such T cell clonal expansion was observed to peak at day 25 an d by 90 days had markedly diminished despite the continuing presence o f extensive histologic infiltration. An additional immunization with m Tg at 63 days failed to maintain the mTcR V(beta)13 clonal presence. F urther confirmation of these observations was obtained by direct analy sis of intrathyroidal T cells rescued from mice with EAT. Such intrath yroidal T cells, 25 days after mTg, demonstrated a marked increase in mTcR V13 expressing T cells to 9.4% compared to 2% of T cells in perip heral blood. It appeared, therefore, that in EAT the accumulation of V 13 expressing T cells was a transient phenomenon which peaked at 25 da ys after immunization. The persistence of an intrathyroidal infiltrati on indicated that such T cells must have been accompanied by the accum ulation and recruitment of additional selected bystander T cells. Such non-specific T cells may also have an integral role in the progressio n of autoimmune thyroiditis.