Perforin is a secreted protein synthesized by activated cytotoxic T lymphocytes (CTL) and natural killer (NK) cells. It is a key component of the lytic machinery of these cells, being able to insert into the plasma membrane of targeted cells, forming a pore which leads to their destruction. Here we analyse the synthesis, processing and intracellular transport of perforin in the NK cell line YT....

The Ca(2+) sensor synaptotagmin (Syt) VII regulates the exocytosis of conventional lysosomes in several cell types. In CTLs, the Ca(2+)-regulated exocytosis of lytic granules/secretory lysosomes is responsible for the perforin/granzyme-mediated lysis of target cells. To investigate the role of Syt VII in CTL effector function, the expression and function of Syt VII were examined in wild-type an...

BACKGROUND Allograft rejection remains a major obstacle to long-term survival in heart transplantation. Recent studies have demonstrated that apoptotic cell death may occur in acute allograft rejection. The purpose of this study was to determine whether apoptotic cell death is involved in rat cardiac allograft rejection through both the perforin/granzyme pathway and the Fas/Fas ligand (Fas-L) p...

We have recently shown that effector T cells (T(E)) lacking either perforin or IFN-gamma are highly effective mediators of tumor regression. To rule out compensation by either mechanism, T(E) deficient in both perforin and IFN-gamma (perforin knockout (PKO)/IFN-gamma knockout (GKO)) were generated. The adoptive transfer of PKO/GKO T(E) mediated complete tumor regression and cured wild-type anim...

Rev Bras Hematol Hemoter. 2011;33(4):250-8 3. Liu Z, Cumberland WG, Hultin LE, Prince HE, Detels R, Giorgi JV. Elevated CD38 antigen expression on CD8+ T cells is a stronger marker for the risk of chronic HIV disease progression to AIDS and death in the Multicenter AIDS Cohort Study than CD4+ cell count, soluble immune activation markers, or combinations of HLA-DR and CD38 expression. J Acquir ...

Interactions between inducible co-stimulatory molecule (ICOS) and ICOS-ligand (ICOS-L) are crucial for T-cell co-stimulation, effector cell differentiation and memory CD8+ T-cell activation. Because in the muscle of patients with sporadic inclusion body myositis (sIBM) clonally expanded CD8+ T cells invade major histocompatibility complex (MHC) class I-expressing muscle fibres, we investigated ...

Abstract Contact hypersensitivity (CHS) is a CD8 T cell mediated response to hapten skin sensitization and challenge. Hapten-primed infiltration into the challenge site during elicitation of CHS requires prior activation novel population Gr-1 +CXCR2 +cells expressing FasL perforin. The goal these studies was further characterize this myeloid-derived cells determine mechanisms generating in bone...

Several products of CTL and NK cells, including a pore-forming protein (PFP;t perforin or cytolysin) (1-4) and several serine esterases (SE) (5-12), have been cloned and sequenced . These proteins are localized to cytoplasmic granules and represent the known structural components ofthe pore-formation and granule exocytosis models for cell-mediated killing (13-17). Granule mediators are expresse...

The maturation of naive CD8(+) T cells into effector CTLs is a critical feature of a functional adaptive immune system. Development of CTLs depends, in part, upon the expression of the transcriptional regulator eomesodermin (EOMES), which is thought to regulate expression of two key effector molecules, perforin and granzyme B. Although EOMES is important for effector CTL development, the precis...