The Journal of Experimental Medicine
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Published online 27 March 2006 doi:10.1084/jem.20052237
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 4, 919-932
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ARTICLE

 Secondary memory CD8+ T cells are more protective but slower to acquire a central–memory phenotype

Ali Jabbari1 and John T. Harty1,2

1 Interdisciplinary Graduate Program in Immunology and 2 Department of Microbiology, University of Iowa, Iowa City, IA 52242

CORRESPONDENCE John T. Harty: john-harty{at}uiowa.edu

The formation of memory CD8 T cells is an important goal of vaccination. However, although widespread use of booster immunizations in humans generates secondary and tertiary CD8 T cell memory, experimental data are limited to primary CD8 T cell memory. Here, we show that, compared with primary memory CD8 T cells, secondary memory CD8 T cells exhibit substantially delayed conversion to a central–memory phenotype, as determined by CD62L expression and interleukin (IL)-2 production. This delayed conversion to a central–memory phenotype correlates with reduced basal proliferation and responsiveness to IL-15, although in vitro coculture with a high concentration of IL-15 is capable of inducing proliferation and CD62L upregulation. Functionally, secondary memory CD8 T cells are more protective in vivo on a per cell basis, and this may be explained by sustained lytic ability. Additionally, secondary memory CD8 T cells are more permissive than primary memory CD8 T cells for new T cell priming in lymph nodes, possibly suggesting a mechanism of replacement for memory T cells. Thus, primary and secondary memory CD8 T cells are functionally distinct, and the number of encounters with antigen influences memory CD8 T cell function.

Abbreviations used: LCMV, lymphocytic choriomeningitis virus; NP, nucleoprotein; TCM, central–memory T cell; TEM, effector–memory T cell; tg, trangenic.


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