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International Immunology, Vol. 13, No. 4, 411-419, April 2001
© 2001 Japanese Society for Immunology

Suicide induced by cytolytic activity controls the differentiation of memory CD8+ T lymphocytes

Joseph T. Opferman1,4, Bertram T. Ober2,4, Ramya Narayanan4 and Philip G. Ashton-Rickardt1,4

1 Committee on Immunology,
2 Department of Pathology and
3 Ben May Institute for Cancer Research, University of Chicago, Chicago, IL 60637, USA
4 Gwen Knapp Center for Lupus and Immunology Research, Chicago, IL60637, USA

Correspondence to: P. G. Ashton-Rickardt, R414, Gwen Knapp Center for Lupus and Immunology Research, 924 East 57th Street, Chicago, IL 60637, USA

Cytotoxic T lymphocytes (CTL) confer protection against intracellular pathogens, yet the mechanism by which some escape activation induced cell death (AICD) and give rise to long-lived memory cells is unclear. We studied the differentiation of transgenic TCR CD8+ cells into CTL and memory cells using a novel system that allowed us to control cytolytic activity. The perforin/granzyme granules used to lyse targets induced the apoptosis of CTL in a fratricide-independent manner. After adoptive transfer to antigen-free mice, the ability of CTL to give generate memory cells was determined. We found that the extent of cytolysis by a common pool of CTL controlled the differentiation into memory cells, which were only generated under conditions of minimal cytolytic activity. Thus, the differentiation of naive CD8+ cells into memory cells may not depend on the presence on a subset of committed CTL precursors, but rather is controlled by the extent of granule-mediated cytolysis.

Keywords: apoptosis, cytotoxic T lymphocytes, immunological memory

Transmitting editor: C. B. Thompson


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