Listeria monocytogenes is a facultative intracellular pathogen that re
plicates inside mononuclear phagocytes and induces specific cellular i
mmunity. Listeriosis encompasses many clinical syndromes and meningiti
s is the most frequent clinical manifestation. Human alpha/beta and ga
mma/delta T cells have been shown to respond to L. monocytogenes antig
ens and to play an important role in resistance against listerial infe
ction. We investigated the nature of listerial ligands and the influen
ce of the major virulence factor, listeriolysin (hly), on the stimulat
ion of human gamma/delta T cells from healthy individuals. We found th
at a listerial somatic protein ligand, which is sensitive to proteinas
e treatment, stimulated gamma/delta T cells in vitro; the majority of
Listeria-responsive gamma/delta T cells expressed V gamma 9V delta 2 T
-cell receptor chains and human leucocyte antigen-DR molecules; gamma/
delta T-cell responses to hly(+) and hly(-) Listeria strains were comp
arable; L. monocytogenes strains of different virulence stimulated gam
ma/delta T cells equally. Thus, protein components of L. monocytogenes
unrelated to virulence activate human gamma/delta T cells in vitro.