Scholarship in Review 86(1)

Scholarship in Review was a magazine highlighting research and scholarly activities at Central Washington University, published by the Office of Graduate Studies and Research.https://digitalcommons.cwu.edu/scholarship_in_review/1002/thumbnail.jp

The regulation of FasL expression during activation-induced cell death (AICD)

Activation-induced cell death (AICD), a Fas ligand (FasL)-dependent pathway, is important for maintaining T-cell homeostasis. Interleukin-2 (IL-2), an enhancer of AICD, can also enhance FasL expression. However, we show that the level of FasL or FLIP protein did not correlate with the susceptibility to AICD. Some T cells expressed high levels of FasL yet failed to undergo AICD, while others expressed little FasL and were sensitive. AICD susceptibility did not correlate with the kinetics of FasL up-regulation or down-regulation. The down-regulation of FasL can be mediated by a metalloprotease. However, we describe an alternative mechanism for the loss of FasL by endocytosis. Endocytosis inhibitors such as cytochalasins, sodium azide, deoxyglucose, or low temperatures prevented the loss of FasL. KB8301, a metalloprotease inhibitor had no effect on the loss of FasL or AICD in the T cells. Enhancing FasL expression was not crucial for AICD and the down-regulation of FasL proceeded via endocytosis