BACKGROUND: Xenogeneic cellular immune responses are mediated by either direct or indirect pathways depending on the participation of donor or host antigen presenting cells, respectively. The contribution of direct response of human T cells, especially memory T cells, to porcine antigen presenting cells is currently unknown. Here, we sought to determine whether human peripheral blood memory/activated phenotype T cells are directly responsive to porcine endothelial cells. METHODS: Porcine aortic endothelial cells (PAECs) were prepared from Yorkshire or miniature pigs. Highly purified human T cells, including naïve and memory/activated phenotype cells, were incubated with PAECs with or without the addition of exogenous cytokines. T-cell proliferation and T-cell receptor (TCR) Vbeta usage in response to PAECs were analyzed. RESULTS: Both CD8(+) and CD4(+) T cells responded directly to PAECs and exhibited exclusive responsiveness to SLA class I and class II molecules, respectively. Naïve and memory/activated phenotype CD4(+) T cells responded against PAECs, whereas only naïve phenotype CD8(+) T cells contributed to such a response. In addition, both populations of xenogeneic human CD4(+) T cells exhibited similar and diverse V beta usage. CONCLUSION: Due to the considerable contribution of human CD45RO(+)CD4(+) T cells to the xenoreactivity against PAECs, effective control of xenogeneic memory/activated T-cell responses would significantly affect long-term survival of transplanted grafts.
BACKGROUND: Xenogeneic cellular immune responses are mediated by either direct or indirect pathways depending on the participation of donor or host antigen presenting cells, respectively. The contribution of direct response of human T cells, especially memory T cells, to porcine antigen presenting cells is currently unknown. Here, we sought to determine whether human peripheral blood memory/activated phenotype T cells are directly responsive to porcine endothelial cells. METHODS: Porcine aortic endothelial cells (PAECs) were prepared from Yorkshire or miniature pigs. Highly purified human T cells, including naïve and memory/activated phenotype cells, were incubated with PAECs with or without the addition of exogenous cytokines. T-cell proliferation and T-cell receptor (TCR) Vbeta usage in response to PAECs were analyzed. RESULTS: Both CD8(+) and CD4(+) T cells responded directly to PAECs and exhibited exclusive responsiveness to SLA class I and class II molecules, respectively. Naïve and memory/activated phenotype CD4(+) T cells responded against PAECs, whereas only naïve phenotype CD8(+) T cells contributed to such a response. In addition, both populations of xenogeneic humanCD4(+) T cells exhibited similar and diverse V beta usage. CONCLUSION: Due to the considerable contribution of human CD45RO(+)CD4(+) T cells to the xenoreactivity against PAECs, effective control of xenogeneic memory/activated T-cell responses would significantly affect long-term survival of transplanted grafts.