Killed or inactivated vaccines targeting intracellular bacterial and protoz
oal pathogens are notoriously ineffective at generating protective immunity
. For example, vaccination with heat-killed Listeria monocytogenes (HKLM) i
s not protective, although infection with live L. monocytogenes induces lon
g-lived, CD8 T cell-mediated immunity. We demonstrate that HKLM immunizatio
n primes memory CD8 T lymphocyte populations that, although substantial in
size, are ineffective at providing protection from subsequent L. monocytoge
nes infection. In contrast to live infection, which elicits large numbers o
f effector CD8 T cells, HKLM immunization primes T lymphocytes that do not
acquire effector functions. Our studies show that it is possible to dissoci
ate T cell-dependent protective immunity from memory T cell expansion, and
that generation of effector T cells may be necessary for long-term protecti
ve immunity.