The CASP8 Knockout Jurkat Polyclonal Cells are a CRISPR/Cas9-edited polyclonal Jurkat T lymphocyte population with targeted disruption of the CASP8 gene, resulting in loss of functional caspase-8. This heterogeneous knockout pool avoids clonal selection bias and provides a robust model for studying caspase-8-dependent signaling in apoptosis, necroptosis, and immune regulation.
Jurkat cells are an immortalized human T lymphocyte line derived from a patient with acute T cell leukemia. Widely used in immunology research, these suspension cells endogenously express death receptors and respond robustly to extrinsic apoptotic stimuli and T cell receptor (TCR) agonists, making them an ideal host for studying death receptor pathways.
Caspase-8 is an initiator caspase central to extrinsic apoptosis. Upon death receptor ligation by FasL, TNF??, or TRAIL, it is recruited via FADD to form the death-inducing signaling complex (DISC), where it undergoes auto-proteolytic activation and subsequently cleaves executioner caspases-3/7. Caspase-8 also suppresses necroptosis by cleaving RIPK1 and modulates NF-??B inflammatory signaling. Its activity is regulated by c-FLIP, TRADD, and interactions with TRAF2, cIAP1/2, and other factors, situating it at a critical node in cell fate determination.
In Jurkat cells, CASP8 knockout abrogates apoptosis induced by FasL, TNF??, or TRAIL, revealing the role of caspase-8 in T cell death. This permits dissection of alternative pathways like necroptosis when apoptosis is blocked. The model is thus invaluable for examining the apoptosis-necroptosis switch and the contribution of caspase-8 to TCR signaling and immune homeostasis.
Applications include apoptosis assays (Annexin V/PI, caspase-3/8 activity), necroptosis induction (TNF??+Smac mimetic+zVAD), western blotting for substrates (caspase-3, BID, RIPK1, PARP), flow cytometry for death receptors and T cell activation, and transcriptomic profiling. These cells support drug screening, immunomodulatory compound evaluation, and studies of ALPS and cancer. For further information, please contact Ascent Research.
