2026-06-28T20:34:37Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/989662025-03-11T16:42:01Zcom_20.500.14352_14col_20.500.14352_15

Cell cycle regulation by FasL and Apo2L/TRAIL in human T-cell blasts. Implications for autoimmune lymphoproliferative syndromes Bosque, Alberto Aguiló, Juan I del Rey, Manuel Paz Artal, Estela Natividad Allende Martínez, Luis Miguel Naval, Javier Anel, Alberto The Fas-FasL pathway plays an important role in the homeostasis of mature lymphocytes, with defects causing autoimmune lymphoproliferative syndromes (ALPS). Human T-cell blasts are not sensitive to FasL or Apo2L/TRAIL-induced apoptosis unless they get reactivated, but either of those ligands inhibits their growth in the absence of cell death induction due to a cell cycle arrest in S-G2/M. In the present work, we have studied the mechanism(s) by which FasL or Apo2L/TRAIL regulate T-cell blast cell cycle in healthy donors and in two types of ALPS patients. Our data indicate that in human CD8+ T-cell blasts, Fas ligation, and especially Apo2L/TRAIL induce the p53-dependent decrease in cyclin-B1 levels. However, the induction of the negative cell cycle regulator p21WAF1 by FasL or Apo2L/TRAIL in either CD4+ or CD8+ T-cell blasts seems to be the main regulatory mechanism. This mechanism is dependent on caspase activation and on H2O2 generation. The increase in p21 levels by FasL or Apo2L/TRAIL is concomitant with p53 increases only in CD8+ T-cell blasts, with p21 levels maintained high for longer times than p53 levels. In CD4+ T-cell blasts p21 levels are controlled through a transient and p53-independent mechanism. The present results suggest that the etiology of ALP syndromes could be related not only to defects in apoptosis induction, but also in cell cycle regulation. 2024-02-05T13:07:09Z 2024-02-05T13:07:09Z 2024-02-05T13:07:09Z 2008 journal article https://hdl.handle.net/20.500.14352/98966 0741-5400 1938-3673 10.1189/jlb.0108043 eng SAF2004-03058 info:eu-repo/grantAgreement/MEC//SAF2007-65144/ES/FUNCION Y REGULACION DE LOS LINFOCITOS T Y LAS CELULAS NK EN DONANTES SANOS Y EN DIVERSAS PATOLOGIAS INMUNITARIAS. ESTUDIO DE LAS MOLECULAS RELEVANTES EN LA INMUNIDAD ANTITUMORAL/ Bosque A, Aguiló JI, del Rey M, Paz-Artal E, Allende LM, Naval J, Anel A. Cell cycle regulation by FasL and Apo2L/TRAIL in human T-cell blasts. Implications for autoimmune lymphoproliferative syndromes. J Leukoc Biol. 2008 Aug;84(2):488-98. doi: 10.1189/jlb.0108043. Epub 2008 May 15. PMID: 18483205. restricted access Oxford Academic