CTL and NK cells cultured in vitro are known to produce a cytolytic pore-forming protein (PFP, perforin) localized in their cytoplasmic granules. Using purified perforin, we showed here that both cloned CTL and primary killer cell populations, including allospecific CTL, NK/lymphokine-activated killer cells, and MHC-non-restricted CTL, were more resistant to perforin-mediated killing than other...

Missense mutations in perforin, a critical effector of lymphocyte cytotoxicity, lead to a spectrum of diseases, from familial hemophagocytic lymphohistiocytosis to an increased risk of tumorigenesis. Understanding of the impact of mutations has been limited by an inability to express human perforin in vitro. We have shown, for the first time to our knowledge, that recombinant human perforin is ...

CTL and NK cells cultured in vitro have been shown to contain a cytolytic pore-forming protein (PFP/perforin/cytolysin). To date, it has not been determined whether perforin is expressed by CTL that have been primed in vivo. Here, we have infected mice with two strains of lymphocytic choriomeningitis virus (LCMV), one of which mainly produces choriomeningitis and, the other, hepatitis. Brain an...

epstein-barr virus (ebv) is a ubiquitous human -herpesvirus that infects about 95% of the adult population. the majority of primary infections occurs in early childhood and is generally subclinical; it can cause infectious mononucleosis (im), which is usually a self-limiting lymphoproliferative disorder. however, infection of ebv occasionally results in severe, often lethal diseases, which inc...

Abstract Biomechanics is a fundamental feature of cell. However, the manner by which actomysin tension affects tumor immune evasion remains unclear. Here we show that although cytotoxic T lymphocytes (CTL) can effectively destroy stiff differentiated cells, they fail to kill soft tumor-repopulating cells (TRC). TRC softness prevented membrane pore formation caused CTL-released perforin. Perfori...

255 PRF deficiency occurs not only with allelic variants characterized by mutations in the coding region of the gene. McIlroy et al. reported that the occurrence of a C/T polymorphism at position-398 of the proximal promoter region of the PRF1 gene was associated with decreased quantities of PRF in CTLs in HIV infected patients. A decrease of about 50% of control PRF levels was observed in hete...

CD8+ T cells were previously shown to be important in preventing lymphoproliferation and immunodeficiency following infection of murine AIDS (MAIDS)-resistant mice with the LP-BM5 mixture of murine leukemia viruses. To further evaluate the mechanisms contributing to MAIDS resistance, we studied mice lacking CD8+ T cells or deficient in perforin due to knockout of the beta2-microglobulin (beta2M...

Mouse NK cells may use both cytokine, e.g. IFN-gamma, tumor necrosis factor (TNF)-alpha and IL-12, and cytotoxic, e.g. perforin and Fas-FasL, pathways to reject incompatible bone marrow cell (BMC) grafts. To begin a dissection of these two major pathways, mice bearing deletional mutations of IFN-gamma, TNF-RI/II or perforin, or mice treated with mAb to IL-12, IFN-gamma or NK1.1 were irradiated ...