HLA-CW3 EXPRESSION ON PORCINE ENDOTHELIAL-CELLS PROTECTS AGAINST XENOGENEIC CYTOTOXICITY MEDIATED BY A SUBSET OF HUMAN NK CELLS

Citation
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
Citations number
40
Categorie Soggetti
Immunology
Journal title
The Journal of immunology
ISSN journal
00221767 → ACNP
Volume
159
Issue
7
Year of publication
1997
Pages
3655 - 3661
Database
ISI
SICI code
0022-1767(1997)159:7<3655:HEOPEP>2.0.ZU;2-T
Abstract
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.