Granzymes are the essential downstream effector molecules for the control of primary virus infections by cytolytic leukocytes.
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| 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 gzmAxgzmB 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.
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| Authors | A Müllbacher, P Waring, R Tha Hla, T Tran, S Chin, T Stehle, C Museteanu, M M Simon |
| Journal | Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 96 Issue 24 Pg. 13950-5 (Nov 23 1999) ISSN: 0027-8424 [Print] United States |
| PMID | 10570179 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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