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Differential Survival of Cytotoxic T Cells and Memory Cell Precursors¹

Manling Zhang^2,*, Susan Byrne^2,*, Ni Liu^2,*, Yue Wang^2,*, Annette Oxenius and Philip G. Ashton-Rickardt^2,3,*

^* Department of Pathology, Ben May Institute for Cancer Research and Committee on Immunology, University of Chicago, Chicago, IL 60637; and Institute of Microbiology, Eidgenössische Technische Hochschule, Zurich, Switzerland

It is widely assumed that the development of memory CD8 T cells requires the escape of CTLs from programmed cell death. We show in this study that although serine protease inhibitor 6 (Spi6) is required to protect clonal bursts of CTLs from granzyme B-induced programmed cell death, it is not required for the development of memory cells. This conclusion is reached because memory cell precursors down-regulate both Spi6 and granzyme B, unlike CTLs, and they do not require Spi6 for survival. These findings suggest that memory CD8 T cells are derived from progenitors that are refractory to self-inflicted damage, rather than derived from fully differentiated CTLs.

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 Institutes of Health Grant AI45108 (to P.G.A.-R.).

² Current address: Department of Immunology, Division of Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, W12 0NN London, U.K.

³ Address correspondence and reprint requests to Dr. Philip G. Ashton-Rickardt at the current address: Department of Immunology, Division of Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, W12 0NN London, U.K. E-mail address: p.ashton-rickardt{at}imperial.ac.uk

⁴ Abbreviations used in this paper: GrB, granzyme B; PCD, programmed cell death; LCMV, lymphocytic choriomeningitis virus; ICS, intracellular staining; Spi6, serine protease inhibitor 6; KO, knockout.

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