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

Background. Dendritic cells (DC) are the most potent antigen-presenting cel ls in the immune system. To define the role of human DC in human anti-porci ne immune responses, we defined the interaction of human DC with porcine ao rtic endothelial cells (PAEC). Methods. To determine the immune responses, both monocyte-derived and perip heral blood DC were cultured with porcine and human endothelial cells. We a nalyzed the role of CD11a, CD11b, and CD54 in a cell-to-cell adhesion assay using antibodies against these molecules. The expression pattern of costim ulatory molecules (CD40, CD80, CD86), adhesion molecules (CD54), and intrac ellular cytokines (interleukin-12p70 and tumor necrosis factor [TNF]-alpha) in DC after interaction with endothelial cells was determined by immunoflu orescence. Results. Human DC significantly adhered to PAEC (38-40%), and this adhesion was augmented (> 50%) upon treatment with either recombinant swine interfe ron-gamma or recombinant human TNF-alpha. Addition of human DC to PAEC was blocked by pretreatment of DC with antibodies specific to human leukocyte f unction-associated antigen-1 or CD54. Adhesion of DC to PAEC also resulted in the activation of DC, which was manifested by up-regulation of costimula tory molecules (CD40, CD80, CD86), adhesion molecules (CD54), and HLA-DR. P AEC-activated human DC provided proliferative signals to the naive autologo us CD4(+) T cells and synthesized interleukin-12p70 and TNF-alpha. However, activated DCs failed to lyse PAEC in such interaction. Conclusion. Human DC effectively adhered to PAEC and were activated by xeno antigen, resulting in highly efficient antigen presentation and proliferati on of CD4(+) T cells. Further, this interaction of human DC to PAEC is regu lated by the participation of costimulatory and adherence molecules and cyt okines.