G. Sconocchia et al., CD44 IS A CYTOTOXIC TRIGGERING MOLECULE IN HUMAN PERIPHERAL-BLOOD NK CELLS, The Journal of immunology, 153(12), 1994, pp. 5473-5481
Previous studies have shown that target cells that bind to CD44 adhesi
on molecules on cloned cytotoxic T cells are lysed by the CTL. To dete
rmine whether CD44 is also a cytotoxic trigger molecule in human PBL,
we tested a bispecific Ab consisting of anti-CD44 Fab cross-linked to
a Fab against a target cell Ag, in cytotoxicity assays using PBL as ef
fecters. We found that PBL mediated lysis in the presence of the anti-
CD44 bispecific Ab provided that the effector cells were stimulated wi
th either IL-2 or IL-12. Cell fractionation experiments showed that CD
44-directed cytolysis was mediated exclusively by CD56(+) low buoyant
density cells, mainly by NK(CD16(+)) cells, but also to a lesser exten
t by CD56(+) T cells. CD44-directed cytolysis appeared in these subset
s 24 to 48 h after addition of IL-2 and paralleled the acquisition of
Ab-independent (LAK) activity; in contrast, these cells mediated Ab-de
pendent cellular cytotoxicity and CD3 redirected lysis before stimulat
ion with IL-2. Unstimulated CD56(+) cells uniformly expressed high lev
els of CD44 that increased modestly after incubation with IL-2. No cha
nges in isoform expression in the extracellular domain of CD44 could b
e detected upon activation with the use of isoform-specific mAbs. Thus
, lymphokine stimulation caused CD44 to become a cytotoxic trigger in
subsets of PBL that mediated other forms of cytotoxicity and expressed
CD44 before activation, suggesting that activation of these cells was
accompanied by a coupling of CD44 to their lytic machinery.