Secretory lysosomes of natural killer (NK) cells, containing perforin and granzymes, are indispensable for NK-cell cytotoxicity because their release results in the induction of target-cell apoptosis. Lysosome-associated membrane protein (LAMP) 1/CD107a is used as a marker for NK-cell degranulation, but its role in NK-cell biology is unknown. We show that LAMP1 silencing causes inhibition of NK...

The host-encoded Perforin-2 (encoded by the macrophage-expressed gene 1, Mpeg1), which possesses a pore-forming MACPF domain, reduces the viability of bacterial pathogens that reside within membrane-bound compartments. Here, it is shown that Perforin-2 also restricts the proliferation of the intracytosolic pathogen Listeria monocytogenes Within a few hours of systemic infection, the massive pro...

Human T-cell Lymphotropic Virus Type I (HTLV-I) primarily infects CD4+ helper T cells. HTLV-I infection is clinically linked to the development of Adult T-cell Leukemia/Lymphoma and of HTLV-I Associated Myelopathy/Tropical Spastic Paraparesis, among other illnesses. HTLV-I transmission can be either horizontal through cell-to-cell contact, or vertical through mitotic division of infected CD4+ T...

OBJECTIVE Perforin is an important component of the death machinery of cytotoxic T cells (CTL). To evaluate functional differences between HIV- and cytomegalovirus (CMV)-specific CTL of coinfected patients, the frequencies of the respective perforin-expressing T cells were analysed in a rapid whole blood assay. METHODS Whole blood of HIV- and CMV-infected individuals was specifically stimulat...

BACKGROUND AND OBJECTIVES The aim of this study was to assess the feasibility of high-dose chemotherapy plus autologous hematopoietic stem cell transplantation (HDC/AHSCT) in AIDS-related lymphoma (ARL), and its long-term impact in patients with human immunodeficiency virus (HIV) treated with highly active antiretroviral therapy (HAART). DESIGN AND METHODS Fourteen patients with relapsed or r...

hemophagocytic lymphohistiocytosis (hlh) is an aggressive and potentially life-threatening disease and has to be considered in the differential diagnosis of many conditions. hlh comprises two different conditions that are difficult to differentiate; familial hemophagocytic lymphohistiocytosis (fhlh) or familial erythrophagocytic lymphohistiocytosis (fel), and secondary hemophagocytic syndromes ...

Cytotoxic lymphocytes trigger apoptosis by releasing perforin and granzymes (Grn). GrnB activates the caspase apoptotic pathway, but little is known about GrnA-induced cell death. Perforin was used to load recombinant GrnA and GrnB and enzymatically inactive variants into target cells. GrnA induces single-strand DNA breaks that can be labeled with Klenow polymerase and visualized on alkaline ge...

Antigen-Specific CD8 T Cell Homeostasis Badovinac et al. (1) reported important new insights concerning the role of perforin and interferon-g (IFN-g) in regulating antigenspecific (Ag-specific) CD8 T cell homeostasis. Using an attenuated strain of Listeria monocytogenes, they demonstrated that absence of perforin resulted in increased levels of specific CD8 T cells, whereas absence of IFN-g con...

Development of the ancient innate immune system required not only a mechanism to recognize foreign organisms from self but also to destroy them. Pore-forming proteins containing the membrane attack complex Perforin domain were one of the first triumphs of an innate immune system needing to eliminate microbes and virally infected cells. Membrane attack complex of complement and Perforin domain p...