Fas/Fas ligand-driven T cell apoptosis as a consequence of ineffective thyroid immunoprivilege in Hashimoto's thyroiditis

Giorgio Stassi, Matilde Todaro, Fabio Bucchieri, Antonella Stoppacciaro, Felicia Farina, Giovanni Zummo, Roberto Testi, Ruggero De Maria

Research output: Contribution to journalArticle

Abstract

Hashimoto's thyroiditis (HT) is a chronic autoimmune disease resulting from Fas-mediated thyrocyte destruction. Although autocrine/paracrine Fas- Fas ligand (FasL) interaction is responsible for thyrocyte cell death during the active phases of HT, the role of infiltrating T lymphocytes (ITL) in this process is still unknown. Therefore, we investigated the expression and function of Fas and FasL in ITL. All ITL expressed high levels of Fas and CD69, an early marker of T cell activation associated with functional Fas expression in T cells in vivo. In contrast to thyrocytes that were found to produce high levels of FasL, ITL did not express significant amounts of FasL, suggesting that ITL are not directly involved in thyrocyte destruction. The analysis of ITL purified from HT thyroids showed that ITL were massively killed by Fas crosslinking and that a considerable number (24-36%) underwent spontaneous apoptosis within 36 b of culture. Accordingly, in situ TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) staining revealed that a significant number (10-15%) of ITL in proximity to FasL- producing thyroid follicles were apoptotic. Moreover, virtually all ITL in proximity to thyroid follicles were preapoptotic, as they expressed high levels of GD3 ganglioside, a killer glycolipid responsible for the generation of irreversible apoptotic signals that accumulate in hematopoietic cells shortly after Fas crosslinking. These data demonstrate that ITL are not directly involved in thyrocyte cell death during HT, suggesting that autocrine/paracrine Fas-FasL interaction is a major mechanism in autoimmune thyrocyte destruction.

Original languageEnglish
Pages (from-to)263-267
Number of pages5
JournalJournal of Immunology
Volume162
Issue number1
Publication statusPublished - Jan 1 1999

ASJC Scopus subject areas

  • Immunology

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    Stassi, G., Todaro, M., Bucchieri, F., Stoppacciaro, A., Farina, F., Zummo, G., Testi, R., & De Maria, R. (1999). Fas/Fas ligand-driven T cell apoptosis as a consequence of ineffective thyroid immunoprivilege in Hashimoto's thyroiditis. Journal of Immunology, 162(1), 263-267.