T Cell Receptor Vβ Usage in Murine Experimental Autoimmune Thyroiditis

Abstract

Mouse thyroglobulin (MTg)-sensitized spleen cells activatedin vitrowith MTg induce experimental autoimmune thyroiditis (EAT) in which the thyroid infiltrate consists primarily of mononuclear cells (MNC) (lymphocytic EAT). MTg-sensitized spleen cells cultured with MTg together with anti-IL2R antibody induce a granulomatous form of EAT in which the thyroid is infiltrated by MNC in addition to PMNs, histiocytes, and multinucleated giant cells. CD4+T cells are the primary effector cells for both forms of EAT. The presence of specific T cell receptor (TCR) Vβ families in the thyroid infiltrate was examined by flow cytometry and reverse transcription–polymerase chain reaction (RT–PCR) amplification of mRNA. At the time of maximal disease severity, cells infiltrating the thyroid expressed primarily Vβ8, Vβ4, Vβ11, and Vβ14 as determined by flow cytometry. RT–PCR confirmed these findings and also detected several additional Vβ gene families, including Vβ1, Vβ2, Vβ6, Vβ13, and Vβ15; Vβ3, Vβ10, and Vβ12 were also detected in some, but not all, experiments. There were no differences in the Vβ T cell repertoires in thyroids of mice with lymphocytic vs granulomatous EAT. RT–PCR analysis of intrathyroidal MNC 11 days after cell transfer showed TCR Vβ mRNA transcripts to be primarily restricted to Vβ4, Vβ11, and Vβ14, whereas the predominant thyroid-infiltrating T cell 21 days after cell transfer was Vβ8+. Depletion of Vβ8+T cells in recipient mice did not reduce EAT severity. TCR Vβ usage shifted predominantly to Vβ4+, Vβ11+, or Vβ14+T cells of both CD4+and CD8+T cell subsets. These results indicate that multiple Vβ TCR are expressed in thyroids of mice with EAT.