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 h 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.