Mr. Zocchi et al., HIV-1 TAT INHIBITS HUMAN NATURAL-KILLER-CELL FUNCTION BY BLOCKING L-TYPE CALCIUM CHANNELS, The Journal of immunology (1950), 161(6), 1998, pp. 2938-2943
Herein we show that functional phenylalkylamine-sensitive L-type calci
um channels are expressed by human NK cells and are involved in the ki
lling of tumor targets, Blocking of these channels by phenylalkylamine
drugs does not affect effector/target cell binding but inhibits the r
elease of serine esterases responsible for cytotoxicity. Interestingly
, treatment of NK cells with HIV-1 Tat, which is known to affect sever
al calcium-mediated events in immune cells, impairs their cytotoxic ac
tivity. In addition, Tat inhibits the rise in intracellular free calci
um concentration upon cross-linking of the adhesion molecule CD11a, en
gaged during effector/target cell interaction, and the activation mole
cule CD16, Exogenous Tat does not influence NK-target cell binding but
prevents NK cell degranulation, We propose that the molecular structu
re(s) on NK cells mediating the inhibitory effects HIV-1 Tat belong to
L-type calcium channels, based on three lines of evidence: 1) binding
of phenylalkylamine derivatives to these channels is cross-inhibited
by Tat; 2) L-type calcium channels from NK cell lysates bind to Tat li
nked to Sepharose columns; 3) the inhibitory effect of HIV-1 Tat on NK
cell function is prevented by the agonist of L-type calcium channels,
Bay K 8644, Altogether, these results suggest that exogenous Tat is d
eeply involved in the impairment of NK cell function during HIV-1 infe
ction.