Activation of human dendritic cells by porcine aortic endothelial cells: Transactivation of naïve T cells through costimulation and cytokine generation

Background. Dendritic cells (DC) are the most potent antigen-presenting cells in the immune system. To define the role of human DC in human anti-porcine immune responses, we defined the interaction of human DC with porcine aortic endothelial cells (PAEC). Methods. To determine the immune responses, both monocyte-derived and peripheral blood DC were cultured with porcine and human endothelial cells. We analyzed the role of CD11a, CD11b, and CD54 in a cell-to-cell adhesion assay using antibodies against these molecules. The expression pattern of costimulatory molecules (CD40, CD80, CD86), adhesion molecules (CD54), and intracellular cytokines (interleukin-12p70 and tumor necrosis factor [TNF]-α) in DC after interaction with endothelial cells was determined by immunofluorescence. Results. Human DC significantly adhered to PAEC (38-40%), and this adhesion was augmented (>50%) upon treatment with either recombinant swine interferon-γ or recombinant human TNF.α. Addition of human DC to PAEC was blocked by pretreatment of DC with antibodies specific to human leukocyte function-associated antigen-1 or CD54. Adhesion of DC to PAEC also resulted in the activation of DC, which was manifested by up-regulation of costimulatory molecules (CD40, CD80, CD86), adhesion molecules (CD54), and HLA-DR. PAEC-activated human DC provided proliferative signals to the naive autologous CD4⁺ T cells and synthesized interleukin-12p70 and TNF-α. However, activated DCs failed to lyse PAEC in such interaction. Conclusion. Human DC effectively adhered to PAEC and were activated by xenoantigen, resulting in highly efficient antigen presentation and proliferation of CD4⁺ T cells. Further, this interaction of human DC to PAEC is regulated by the participation of costimulatory and adherence molecules and cytokines.