In analyzing mechanisms of protection against intracellular infections
, a series of human CD1-restricted T cell lines of two distinct phenot
ypes were derived. Both CD4(-)-CD8(-) (double-negative)T cells and CD8
(+) T cells efficiently lysed macrophages infected with Mycobacterium
tuberculosis. The cytotoxicity of CD4(-)CD8(-) T cells was mediated by
Fas-FasL interaction and had no effect on the viability of the mycoba
cteria. The CD8(+) T cells lysed infected macrophages by a Fas-indepen
dent, granule-dependent mechanism that resulted in killing of bacteria
. These data indicate that two phenotypically distinct subsets of huma
n cytolytic T lymphocytes use different mechanisms to kill infected ce
lls and contribute in different ways to host defense against intracell
ular infection.