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

Immunology. 2001 Aug;103(4):426-34. doi: 10.1046/j.1365-2567.2001.01264.x.

Abstract

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.

MeSH terms

  • Animals
  • Apoptosis / immunology*
  • Cell Line
  • Down-Regulation / immunology
  • Edetic Acid / pharmacology
  • Endocytosis / drug effects
  • Endocytosis / immunology
  • Enzyme Inhibitors / pharmacology
  • Fas Ligand Protein
  • Interleukin-2 / immunology
  • Ligands
  • Lymphocyte Activation / immunology*
  • Membrane Glycoproteins / metabolism*
  • Metalloendopeptidases / antagonists & inhibitors
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes / immunology*

Substances

  • Enzyme Inhibitors
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Interleukin-2
  • Ligands
  • Membrane Glycoproteins
  • Edetic Acid
  • Metalloendopeptidases