We have shown previously that IL-2-activated splenocytes can inhibit t
he growth of Candida albicans hyphae in vitro. Herein we demonstrate t
hat plastic nonadherent lymphocytes that are CD8(+) mediate the antifu
ngal activity. Enrichment for CD8(+) cells markedly enhanced the antif
ungal activity of the IL-2-activated lymphocyte population for C. albi
cans and the cytotoxic activity of the lymphocytes for an NK-resistant
cell line. Depletion of CD8(+) cells reduced the lymphocyte populatio
n's antifungal activity and cytotoxic activity for the NK-resistant ce
ll line. Enrichment for NK1.1(+) cells markedly reduced the antifungal
activity of the lymphocyte population for C. albicans and increased t
he cytotoxic activity of the lymphocytes for an NK-sensitive cell line
. Depletion of NK1.1(+) cells increased the lymphocyte population's an
tifungal activity and cytotoxic activity for the NK-resistant cell lin
e. Generation of the antifungal lymphocytes in culture required IL-2 a
nd was not replaced with IFN-gamma. These data show that IL-2-activate
d CD8(+) T lymphocytes exert the greatest amount of antifungal effect
against the hyphal form of C. albicans, whereas IL-2- or IFN-gamma-act
ivated NK cells have little or no effect against the hyphae.