Jd. Seebach et al., HLA-CW3 EXPRESSION ON PORCINE ENDOTHELIAL-CELLS PROTECTS AGAINST XENOGENEIC CYTOTOXICITY MEDIATED BY A SUBSET OF HUMAN NK CELLS, The Journal of immunology, 159(7), 1997, pp. 3655-3661
There is increasing evidence that NK cells make an important contribut
ion to human anti-porcine xenogeneic cytotoxicity. Most allogeneic as
well as autologous normal cells are not susceptible to NK cell-mediate
d cytotoxicity because they express inhibitory molecules encoded withi
n the MHC class I loci. The protective signal is delivered to NK cells
through killer cell-inhibitory receptors expressing different MHC cla
ss I specificities, It has been proposed that xenogeneic target cells
may be susceptible to NK cell-mediated lysis because their MHC class I
molecules fail to be recognized by human killer cell-inhibitory recep
tors, To explore this hypothesis, we examined the effect of human MHC
class I expression on porcine target cell lysis by human NK cells, An
immortalized porcine bone marrow-derived endothelial cell line (2A2) w
as transfected with three different human MHC class I allelic genes (H
LA-A2, -B27, or -Cw3), The cytotoxic activity of several CL183(+) NK c
lones, which lysed untransfected porcine cells effectively, was substa
ntially blocked by the presence of HLA-Cw3. In contrast, HLA-Cw3-posit
ive cells were not protected against lysis by CL183(-)EB6(+) NK clones
, The expression of HLA-B27 or HLA-A2 molecules on pig target cells di
d not provide substantial protection from lysis by any of the NK clone
s tested, In addition to confirming the hypothetical basis of NK cell-
mediated killing of xenogeneic targets, these results have practical i
mplications as an approach to overcoming NK cell-mediated cytotoxicity
, which may be an obstacle to pig-to-human xenotransplantation.