Open AccessSuicide induced by cytolytic activity controls the differentiation of memory CD8+ T lymphocytes
Author(s) -
Joseph T. Opferman,
Bertram T. Ober,
Ramya Narayanan,
Philip G. AshtonRickardt
Publication year - 2001
Publication title -
international immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.86
H-Index - 134
eISSN - 1460-2377
pISSN - 0953-8178
DOI - 10.1093/intimm/13.4.411
Subject(s) - cytolysis , ctl* , cytotoxic t cell , perforin , microbiology and biotechnology , cd8 , adoptive cell transfer , biology , granzyme b , immunology , granzyme , antigen , chemistry , t cell , immune system , biochemistry , in vitro
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.