Characterization of human killer cell reactivity against porcine target cells: differential modulation by cytokines

The cytotoxic cell response to porcine cells by human lymphocytes, and the modulation of cytolytic cellular activity by human cytokines were investiga ted. Human peripheral blood mononuclear cells (PBMC) and purified lymphocyt e subsets were co-cultured with fresh irradiated porcine stimulator cells a nd examined for the development of lyric activity and for their proliferati ve response. Porcine target cells included a new cell fine, MS-PBMC-J2 (des ignated J2; SLA-DR+MHC class I(+)CD2(+)CD3(-)CD8(+)CD16(+)CD45(+)), aortic and microvascular endothelial cells. Initial results showed that natural ki ller (NK) cells were fivefold more efficient in killing porcine target cell s compared with T cells, IL-12 augmented the killing of porcine target cell s by human NK cells beyond that induced by stimulation with cells alone. In contrast, IL-2 and IL-15 often induced substantial human NK cell mediated killing of porcine target cells, including endothelial cells in the case of IL-2 where such targets were examined, even in the absence of stimulator c ells. Finally, neither IL-18 nor IL-8 had any effect beyond background on N K cell mediated killing of porcine target cells. These findings show that c ytokines that would be produced in a xenograft setting clearly modulate the ability of human cytolytic cells Co kill porcine targets. In addition, fre sh unstimulated human NK cells lysed J2 and porcine aortic endothelial cell s, but not porcine microvascular endothelial cells, suggesting the possibil ity of rapid attack of xenografts by NK cells, and differential susceptibil ity of endothelial cells from different vascular structures to this attack.