ALTERATION OF ADHESION AND HLA MOLECULES EXPRESSION ON FIBROBLASTS BY NATURAL KILLER (NK) CELLS FROM PATIENTS WITH GRAFT VERSUS HOST DISEASE (GVHD)
Amal Bishara, Sagit Ziv, Arnon Nagler and Chaim Brautbar. Tissue Typing Unit, The Lautenberg Center for General and Tumor Immunology and Dept. of Bone Marrow Transplantation, Hadassah Hospital, Jerusalem, Israel.

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NK cells (CD 16+, CD56+) form a unique group of lymphocytes which differ from T and B subsets in surface phenotype, target cell recognition and function. NK cells are the first cell subset of the immune system to appear post bone marrow transplantation (BMT) and they are the major cell subset present during the development of acute GVHD, in which the skin is the first and the crucial target organ. However the role of NK cells in GVHD is not fully understood. We investigated the interaction between NK cells obtained from GVHD patients (from HLA identical BMT) and human primary fibroblast monolayers by co-culturing them

for up to two weeks. At several time points after co-culturing we evaluated the morphological appearance, adhesion molecule expression and cytoskeleton integrity of the fibroblasts. Addition of NK cells from GVHD patients (n= 10) to the fibroblasts monolayers resulted in adherence of NK cell to the fibroblasts, detachment and reformation in clusters, shrinkage and elongation of the fibroblasts. These morphological changes were accompanied by up-regulation of ICAM-l expression already after 2 hours of incubation, alteration in CD44 expression which was observed after 24-48 hours, up-regulation of HLA class I and induction of HLA class-II. Disruption of the fibroblast cytoskeleton was observed by tubulin staining and scanning with confocal microscopy. Co-culturing of NK cells from GVHD free BM transplants (n=5) did not result in similar findings. In summary, NK cells from GVHD patients induced morphological changes, adhesion and HLA molecules expression alteration in primary fibroblast monolayers.