Molecular mechanisms of immune-mediated lysis of murine renal cancer: differential contributions of perforin-dependent versus Fas-mediated pathways in lysis by NK and T cells.

Fas-Mediated Pathways in Lysis by NK and Contributions of Perforin-Dependent Versus Lysis of Murine Renal Cancer: Differential Molecular Mechanisms of Immune-Mediated Winkler-Pickett and Robert H. Wiltrout

Tumor-specific CTL kill murine renal cancer cells using both perforin and Fas ligand-mediated lysis in vitro, but cause tumor regression in vivo in the absence of perforin.

Kidney cancer is a devastating disease; however, biological therapies have achieved some limited success. The murine renal cancer Renca has been used as a model for developing new preclinical approaches to the treatment of renal cell carcinoma. Successful cytokine-based approaches require CD8(+) T cells, but the exact mechanisms by which T cells mediate therapeutic benefit have not been complet...

Perforin/granzyme-dependent and independent mechanisms are both important for the development of graft-versus-host disease after murine bone marrow transplantation.

Graft-versus-host disease (GvHD) is the major limiting toxicity of allogeneic bone marrow transplantation. T cells are important mediators of GvHD, but the molecular mechanisms that they use to induce GvHD are controversial. Three effector pathways have been described for cytotoxic T lymphocytes: one requires perforin and granzymes, the second Fas (APO-1; CD95) and its ligand. Thirdly, secreted...

New knowledge about T-cell cytotoxicity.

Ever since the initial reports that antigen-specific cytolytic T lymphocytes (CTLs) are generated during allograft rejection or viral infection [1], many attempts have been made to elucidate the precise mechanism(s) by which CTLs destroy target cells. Earlier in vitro studies demonstrated that target-cell lysis requires intimate contact between the CTL and its target and is highly specific, i.e...

Altered peptide ligands trigger perforin- rather than Fas-dependent cell lysis.

CTLs lyse Fas-expressing target cells by the concomitant action of a perforin- and a Fas-dependent mechanism. This study analyzed whether target cells pulsed with T cell antagonists and other altered peptide ligands (APLs) were susceptible selectively to only one of these two mechanisms. In vivo and in vitro activated T cells from transgenic mice expressing a TCR specific for lymphocytic chorio...