Regner, MatthiasPavlinovic, LisaYoung, NicolieMüllbacher, Arno2015-10-272015-10-271932-6203http://hdl.handle.net/1885/16119NK cells kill target cells mainly via exocytosis of granules containing perforin (perf) and granzymes (gzm). In vitro, gzm delivery into the target cell cytosol results in apoptosis, and induction of apoptosis is severely impaired in the absence of gzm A and B. However, their importance for in vivo cytotoxicity by cytotoxic T cells has been questioned. We used an in vivo NK cytotoxicity assay, in which splenocytes from wild-type and β(2)microglobulin-deficient (MHC-I(neg)) mice are co-injected into recipients whose NK cells were activated by virus infection or synthetic Toll-like receptor ligands. Elimination of adoptively transferred MHC-I(neg) splenocytes was unimpaired in the absence of gzmA and gzmB, but dependent on perforin. This target cell rejection was NK cell dependent, since NK cell depletion abrogated it. Furthermore, target cell elimination in vivo was equally rapid in both wild-type and gzmAxB-deficient recipients, with the majority of specific target cells lost from lymphoid tissue within less than one to two hours after transfer. Thus, similar to T cell cytotoxicity, the contribution of gzmA and B to in vivo target cell elimination remains unresolved.This work was supported by the Australian National Health and Medical Research Council and by a government block grant to the John Curtin School of Medical Research.6 pages© 2011 Regner et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.animalscytotoxicity, immunologicfemalegene expression regulationgranzymeshistocompatibility antigens class ikiller cells, naturallymphocyte activationmicemice, inbred c57blperforinsemliki forest virus2011-08-1110.1371/journal.pone.00232522015-12-09