The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
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Published online 29 March 2004 doi:10.1084/jem.20031799
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 7, 925-936
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Immediate Cytotoxicity But Not Degranulation Distinguishes Effector and Memory Subsets of CD8+ T Cells

Petra Wolint1, Michael R. Betts2, Richard A. Koup2, and Annette Oxenius1

1 Institute for Microbiology, Eidgenössische Technische Hochschule Zürich, 8092 Zurich, Switzerland
2 Laboratory of Immunology, Vaccine Research Center/National Institute of Allergy and Infectious Diseases/ National Institutes of Health, Bethesda, MD 20892

Address correspondence to Annette Oxenius, Institute for Microbiology, Eidgenössische Technische Hochschule Zurich, LFV B31.1, Schmelzbergstrasse 7, 8092 Zurich, Switzerland. Phone: 41-1-632-33-17; Fax: 41-1-632-10-98; email: oxenius{at}micro.biol.ethz.ch

CD8+ T cells play a central role in the resolution and containment of viral infections. A key effector function of CD8+ T cells is their cytolytic activity toward infected cells. Here, we studied the regulation of cytolytic activity in naive, effector, and central versus effector memory CD8+ T cells specific for the same glycoprotein-derived epitope of lymphocytic choriomeningitis virus. Our results show that the kinetics of degranulation, assessed by a novel flow cytometric based assay, were identical in effector and both subsets of memory CD8+ T cells, but absent in naive CD8+ T cells. However, immediate cytolytic activity was most pronounced in effector T cells, low in effector memory T cells, and absent in central memory T cells, correlating with the respective levels of cytolytic effector molecules present in lytic granules. These results indicate that an inherent program of degranulation is a feature of antigen-experienced cells as opposed to naive CD8+ T cells and that the ability of CD8+ T cells to induce target cell apoptosis/death is dependent on granule protein content rather than on the act of degranulation itself. Furthermore, these results provide a potential mechanism by which central memory CD8+ T cell–mediated death of antigen-presenting cells within the lymph node is avoided.

Key Words: cytotoxic T cell • central memory • effector memory • lytic granules • virus

Abbreviations used in this paper: APC, allophycocyanin; CFSE, carboxyfluorescein diacetate succinimidyl ester; CHX, cyclohexamide; grB, granzyme B; LAMP, lysosomal associated membrane protein; LCMV, lymphocytic choriomeningitis virus.


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