Engagement of CD44 up-regulates Fas Ligand expression on T cells leading to activation-induced cell death
- 21 November 2006
- journal article
- Published by Springer Science and Business Media LLC in Apoptosis
- Vol. 12 (1), 45-54
- https://doi.org/10.1007/s10495-006-0488-8
Abstract
Activation-induced cell death (AICD) plays a pivotal role in self-tolerance by deleting autoreactive T cells, but a defect of AICD results in expansion of autoreactive T cells and is deeply involved in the pathogenesis of rheumatoid arthritis. Although the process of AICD is mainly mediated by Fas Ligand (FasL)/Fas signaling, it remains unclear what induces FasL expression on T cells. In the present study, we found that CD44 was the most potent stimulator of FasL expression on human peripheral T cells. CD44 cross-linking rapidly up-regulated FasL expression on the T cell surface by delivery from the cytoplasm without new FasL protein synthesis. This up-regulation of FasL was mediated by activation of a tyrosine kinase, IP3 receptor-dependent Ca2+ mobilization and actin cytoskeletal rearrangements. Furthermore, AICD induced by CD3 restimulation was inhibited by hyaluronidase as well as by soluble Fas, indicating an interaction between membrane-bound hyaluronan and the cell surface CD44 was involved in the up-regulation of FasL expression on T cells and subsequent AICD. We therefore propose that the engagement of CD44 on T cells can eliminate autoreactive T cells by expression of FasL and FasL-mediated AICD.Keywords
This publication has 45 references indexed in Scilit:
- Rheumatoid arthritisThe Lancet, 2001
- T-cell anergy and altered T-cell receptor signaling: effects on autoimmune diseaseImmunology Today, 1998
- The Nonobese Diabetic Mouse as a Model of Autoimmune Diabetes: Immune Dysregulation Gets the NODImmunity, 1997
- Inhibition of T cell apoptosis in the rheumatoid synovium.JCI Insight, 1997
- Apoptosis by Death FactorCell, 1997
- Mutations in Fas Associated with Human Lymphoproliferative Syndrome and AutoimmunityScience, 1995
- Dominant interfering fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndromeCell, 1995
- Fas and Fas ligand: lpr and gld mutationsImmunology Today, 1995
- Activation-induced death of mature T cells in the regulation of immune responsesCurrent Opinion in Immunology, 1995
- Activation-induced apoptosis in lymphocytesCurrent Opinion in Immunology, 1994