Prospective study of T cell receptor utilization following the induction of murine thyroiditis.

ABSTRACT

Murine experimental autoimmune thyroiditis (EAT) is a well established model of autoimmune disease initiated by immunization with thyroglobulin. We have previously analyzed the T cell receptor (TcR) V gene families used by the intrathyroidal lymphocytic infiltrate in CBA/J mice with well established thyroiditis EAT and have implicated T cells expressing 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 detecting 17 mouse TcR V beta gene families to examine the heterogeneity of the amplified V-D-J (CDR3) fragments. As previously, the TcR V beta 13 amplifications showed the expression of two similar homogeneous CDR3 sizes consistent with two clonally expanded T cell populations. However, such T cell clonal expansion was observed to peak at day 25 and by 90 days had markedly diminished despite the continuing presence of extensive histologic infiltration. An additional immunization with mTg at 63 days failed to maintain the mTcR V beta 13 clonal presence. Further confirmation of these observations was obtained by direct analysis of intrathyroidal T cells rescued from mice with EAT. Such intrathyroidal 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 peripheral blood. It appeared, therefore, that in EAT the accumulation of V13 expressing T cells was a transient phenomenon which peaked at 25 days after immunization. The persistence of an intrathyroidal infiltration indicated that such T cells must have been accompanied by the accumulation and recruitment of additional selected bystander T cells. Such non-specific T cells may also have an integral role in the progression of autoimmune thyroiditis.