Porcine embryonic brain cell cytotoxicity mediated by human natural killercells

Intracerebral transplantation of porcine embryonic dopamine-producing neuro ns has been suggested as a method to treat patients with Parkinson's diseas e. Even though the br ain is an immunologically privileged site, neuronal x enografts are usually rejected within a few weeks. T cells are important fo r this process, but the exact cellular events leading to rejection are poor ly characterized. Brain cells from ventral mesencephalon of 26-27-day-old p ig embryos were used as target cells in flow cytometry-assessed cytotoxicit y assays using non- and IL-2-activated CD3(-)CD16(+)CD56(+) human natural k iller (NK) cells as effector cells. The ability of human NK cells to kill p ig embryonic brain cells by antibody-dependent cellular cytotoxicity (ADCC) in the presence of nondepleted and anti-Gal alpha 1,3Gal antibody-depleted human blood group AB serum (AB serum) was evaluated using the same assay. Both nondepleted and anti-Gal alpha 1,3Gal antibody depleted AB serum could mediate ADCC of pig embryonic VM cells when human NK cells were used as ef fector cells. Nonactivated NK cells did not show any direct cytotoxic effec t on freshly isolated VM cells, whereas. IL-2-activated NK cells killed app roximately 50% of the VM cells at an effector-to-target ratio of 50:1 in a 4-h cytotoxicity assay. Activation of VM cells by TNF-alpha did nor change their sensitivity to human NK cell cytotoxicity. Human NK cells may thus co ntribute to a cellular rejection of pig neuronal xenografts by ADCC, or fol lowing IL-2 activation, by a direct cytotoxic effect.