Bosque, AlbertoAguiló, Juan Idel Rey, ManuelPaz Artal, Estela NatividadAllende Martínez, Luis MiguelNaval, JavierAnel, Alberto2024-02-052024-02-052008Bosque 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: 18483205.0741-54001938-367310.1189/jlb.0108043https://hdl.handle.net/20.500.14352/98966The 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.engjournal articlehttps://academic.oup.com/jleukbio/article-abstract/84/2/488/6975191?redirectedFrom=fulltext&login=truehttps://pubmed.ncbi.nlm.nih.gov/18483205/restricted access612.017Lymphocyte proliferationLymphocyte homeostasisAutoimmunityDeath receptorsCiencias Biomédicas32 Ciencias Médicas