{'fraction_non_alphanumeric': 0.03843730308758664, 'fraction_numerical': 0.00630119722747322, 'mean_word_length': 5.934497816593886, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
In Vitro and in Vivo Prevention of Human CD8+ CTL‐Mediated Xenocytotoxicity by Pig c‐FLIP Expression in Porcine Endothelial Cells

Overcoming cell‐mediated immunity, especially of human CD8+ CTLs, is important for the success of xenotransplantation. Our group has previously reported that the cytotoxicity of human CD8+ CTLs against pig endothelial cells (PEC) is highly detrimental and mediated in major part by the Fas/FasL apoptotic pathway. Cellular FLICE inhibitory protein (c‐FLIP) was originally identified as an inhibitor of death‐receptor signaling through binding competition with caspase‐8 for recruitment to Fas‐associated via death domain (FADD). Two major c‐FLIP variants result from alternative mRNA splicing: a short, 26‐KDa protein (c‐FLIPS) and a long, 55‐KDa form (c‐FLIPL). The cytoprotective effects of c‐FLIPS/L in xenograft cells remain controversial. This study demonstrates that the overexpression of c‐FLIPS/L genes markedly suppress human CD8+ CTL‐mediated xenocytotoxicity and, in addition, the cytoprotective effects of c‐FLIPL appear to be significantly stronger than those of c‐FLIPS. Furthermore, to prove the prolonged effects of xenograft survival, PEC transfectants with c‐FLIPS/L genes were transplanted under rat kidney capsules. Prolonged survival was elicited from FLIPS/L transfectants, whereas parental PEC was completely rejected through day 5, posttransplant. Thus, intracellular remodeling with the overexpression of c‐FLIPS/L in xenograft cells may avoid innate cellular attacks against xenografts and facilitate long‐term xenograft survival.