Suicide induced by cytolytic activity controls the differentiation of memory CD8(+) T lymphocytes.
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.
Committee on Immunology, Department of Pathology and Ben May Institute for Cancer Research, University of Chicago, Chicago, IL 60637, USA.
J T
JT
Opferman
B T
BT
Ober
R
R
Narayanan
P G
PG
Ashton-Rickardt
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D003594:Cytoplasmic Granules / Q000378:metabolism; D004791:Enzyme Inhibitors; D006182:H-Y Antigen / Q000276:immunology; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054353:Perforin; D010940:Plant Proteins; D052899:Pore Forming Cytotoxic Proteins; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D004791:Enzyme Inhibitors; D006182:H-Y Antigen; D008562:Membrane Glycoproteins; D010940:Plant Proteins; D052899:Pore Forming Cytotoxic Proteins; D011948:Receptors, Antigen, T-Cell; D054353:Perforin; C072496:CMa protein, barley