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Cutting Edge: Rapid and Efficient In Vivo Cytotoxicity by Cytotoxic T Cells Is Independent of Granzymes A and B¹

Matthias Regner^2,*, Lisa Pavlinovic^*, Aulikki Koskinen^*, Nicolie Young^*, Joseph A. Trapani and Arno Müllbacher^*

^* Emerging Pathogens and Vaccines, John Curtin School of Medical Research, Canberra, Australia; and Cancer Immunology Program, Research Division, Peter MacCallum Cancer Centre, East Melbourne, Australia

Cytotoxic T (Tc) cells lyse target cells via exocytosis of granules containing perforin (perf) and granzymes (gzm). In vitro, gzm delivery into the target cell cytosol results in apoptosis, and in the absence of gzm A and B the induction of apoptosis is severely impaired. However, using in vivo Tc cell killing assays, we find that virus-immune, gzm A x B-deficient (gzmAxB^–/–) mice are competent to eliminate adoptively transferred target cells pulsed with an immunodominant Tc cell determinant as rapidly and completely as their wild-type counterparts. Specific target cell elimination occurred with similar kinetics in both spleen and lymph nodes. Thus, neither gzmA nor gzmB are required for rapid and efficient in vivo cytotoxicity by Tc cells.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the National Health and Medical Research Council of Australia.

² Address correspondence and reprint requests to Dr. Matthias Regner, Emerging Pathogens and Vaccines, John Curtin School of Medical Research, Australian National University, General Post Office Box 334, Canberra, Australian Capital Territory 2601, Australia. E-mail address: Matthias.Regner{at}anu.edu.au

³ Abbreviations used in this paper: Tc, cytotoxic T (cell); DDAO, 7-hydroxy-9H-(1,3-dichloro-9,9-dimethylacridin-2-one); ECTV, ectromelia virus; gzm, granzyme; HE, Hampstead egg; KO, knockout; LCMV, lymphocytic choriomeningitis virus; perf, perforin; WT, wild type.