Immediate cytotoxicity but not degranulation distinguishes effector and memory subsets of CD8+ T cells.
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.
Wolint
Petra
P
Institute for Microbiology, Eidgenössische Technische Hochschule Zurich, Schmelzbergstrasse 7, 8092, Switzerland.
Betts
Michael R
MR
Koup
Richard A
RA
Oxenius
Annette
A
D000818:Animals; D000956:Antigens, Viral; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015550:Cell Degranulation; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D007156:Immunologic Memory; D019041:L-Selectin / Q000378:metabolism; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016176:T-Lymphocyte Subsets / Q000276:immunology
D000956:Antigens, Viral; D000939:Epitopes; D019041:L-Selectin