T cell receptor V beta usage in murine experimental autoimmune thyroiditis.
Mouse thyroglobulin (MTg)-sensitized spleen cells activated in vitro with MTg induced 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) V beta 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 V beta 8, V beta 4, V beta 11, and V beta 14 as determined by flow cytometry. RT-PCR confirmed these findings and also detected several additional V beta gene families, including V beta 1, V beta 2, V beta 6, V beta 13, and V beta 15; V beta 3, V beta 10, and V beta 12 were also detected in some, but not all, experiments. There were no differences in the V beta 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 V beta mRNA transcripts to be primarily restricted to V beta 4, V beta 11, and V beta 14, whereas the predominant thyroid-infiltrating T cell 21 days after cell transfer was V beta 8+. Depletion of V beta 8+ T cells in recipient mice did not reduce EAT severity. TCR V beta usage shifted predominantly to V beta 4+, V beta 11+, or V beta 14+ T cells of both CD4+ and CD8+ T cell subsets. These results indicate that multiple V beta TCR are expressed in thyroids of mice with EAT.
McMurray
R W
RW
Department of Internal Medicine, University of Missouri, Columbia, USA.
Hoffman
R W
RW
Tang
H
H
Braley-Mullen
H
H
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D051379:Mice; D008808:Mice, Inbred CBA; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013954:Thyroglobulin / Q000494:pharmacology; D013961:Thyroid Gland / Q000166:cytology / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000276:immunology*
D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013954:Thyroglobulin