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Perforin-dependent apoptosis functionally compensates Fas deficiency in activation-induced cell death of human T lymphocytes
| Content Provider | Scilit |
|---|---|
| Author | Mateo, Véronique Ménager, Mickaël Basile, Genevieve De Saint Stolzenberg, Marie-Claude Roquelaure, Bertrand Andre, Nicolas Florkin, Benoit Deist, Françoise Le Picard, Capucine Fischer, Alain Rieux-Laucat, Frédéric |
| Copyright Year | 2007 |
| Description | Activation-induced cell death (AICD) is involved in peripheral tolerance by controlling the expansion of repeatedly stimulated T cells via an apoptotic Fas (CD95; APO-1)–dependent pathway. The TNFRSF-6 gene encoding Fas is mutated in children suffering from autoimmune lymphoproliferative syndrome (ALPS), which is characterized by lymphoproliferation and autoimmunity. We examined AICD in Fas-deficient T cells from ALPS patients. We showed that primary activated Fas-deficient T cells die by apoptosis after repeated T cell antigen receptor (TCR) stimulation despite resistance to Fas-mediated cell death. This Fas-independent AICD was found to be mediated through a cytotoxic granules-dependent pathway. Cytotoxic granules-mediated AICD was also detected in normal T lymphocytes though to a lesser extent. As expected, the cytotoxic granules-dependent AICD was abolished in T cells from Rab27a- or perforin-deficient patients who exhibited defective granules-dependent cytotoxicity. Supporting an in vivo relevance of the cytotoxic granules-dependent AICD in ALPS patients, we detected an increased number of circulating T lymphocytes expressing granzymes A and B. Altogether, these data indicated that the cytotoxic granules-dependent cell death in ALPS may compensate for Fas deficiency in T lymphocytes. Furthermore, they identified a novel AICD pathway as a unique alternative to Fas apoptosis in human peripheral T lymphocytes. |
| Related Links | http://bloodjournal.hematologylibrary.org/content/110/13/4285.full.pdf |
| Ending Page | 4292 |
| Page Count | 8 |
| Starting Page | 4285 |
| DOI | 10.1182/blood-2007-05-088286 |
| Journal | Blood |
| Issue Number | 13 |
| Volume Number | 110 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 2007-12-15 |
| Access Restriction | Open |
| Subject Keyword | Research and Experimental Medicine Apoptosis Tcr Alps Fas Aicd Autoimmune Lymphocytes Cytotoxic Activation Induced Cell Granules Dependent Journal: Blood (Vol- 122, Issue- 13) |
| Content Type | Text |
| Resource Type | Article |
