Granzymes are the Essential Downstream Effector Molecules for the Control of Primary Virus Infections by Cytolytic Leukocytes
Abstract
Analysis of perforin-deficient mice has identified the cytolytic pathway and perforin as the preeminent effector molecule in T cell-mediated control of virus infections. In this paper, we show that mice lacking both granzyme A (gzmA) and granzyme B (gzmB), which are, beside perforin, key constituents of cytolytic vesicles, are as incapable as are perforin-deficient mice of controlling primary infections by the natural mouse pathogen ectromelia, a poxvirus. Death of gzmA×gzmB double knockout mice occurred in a dose-dependent manner, despite the expression of functionally active perforin and the absence of an intrinsic defect to generate splenic cytolytic T cells. These results establish that both gzmA and gzmB are indispensable effector molecules acting in concert with perforin in granule exocytosis-mediated host defense against natural viral pathogens.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- November 1999
- DOI:
- 10.1073/pnas.96.24.13950
- Bibcode:
- 1999PNAS...9613950M