The active role played by xenogeneic endothelial cells in the indirect presentation pathway is not lymphocyte trans-co-stimulation.

The human CD4+ T lymphocyte response to major histocompatibility complex (MHC) class II-negative porcine endothelial cells is dependent on the presence of human monocytes through a human leukocyte antigen (HLA) class II-restricted indirect presentation pathway. Because the role of porcine endothelial cells had been previously shown to do more than simply supply xenopeptides, co-stimulatory signals were analysed. Endothelial cells were shown to express the CD54, CD58, CD59 and CD86 transcripts; however, no membrane B7 molecule could be detected. Blocking experiments in a direct pathway model confirmed that porcine endothelial cells could provide co-stimulatory signals to human T cells through the CD2 and LFA-1 pathways. Nevertheless, the proliferation achieved in the indirect presentation model required co-stimulation by LFA-1, CD2 and CD28, engaged by co-stimulation molecules expressed in the cis-form by the human monocytes. These results clearly show that the active role played by the endothelial cells in the indirect pathway is not lymphocyte trans-co-stimulation and suggest that cis-co-stimulation dominates trans-co-stimulation when both are present.