Cytolytic T Lymphocytes (CTLs) kill intracellular pathogens by a granu
le-dependent mechanism. Granulysin, a protein found in granules of CTL
s, reduced the viability of a broad spectrum of pathogenic bacteria, f
ungi, and parasites in vitro. Granulysin directly killed extracellular
Mycobacterium tuberculosis, altering the membrane integrity of the ba
cillus, and, in combination with perforin, decreased the viability of
intracellular M. tuberculosis. The ability of CTLs to kill intracellul
ar M, tuberculosis was dependent on the presence of granulysin in cyto
toxic granules, defining a mechanism by which T cells directly contrib
ute to immunity against intracellular pathogens.