The induction of major histocompatibility complex class II expression is sufficient for the direct activation of human CD4+T cells by porcine vascular endothelial cells

Background. The role played by major histocompatibility complex (MHC) class II-positive vascular endothelial cells in organ graft rejection is unknown but potentially very important. Methods. The MHC class II-negative porcine vascular endothelial cell line P IEC was stably transfected with the human class II transactivator CIITA, in order to induce MHC class II expression without the coinduction of T-cell costimulatory ligands. These PIEC cells were compared with interferon gamma -treated PIEC cells for their capacity to stimulate the proliferation of pu re human CD4+ T cells. Results, The CIITA-transfected PIECs were as effective as interferon gamma- treated PIECs for stimulating unprimed human CD4+ T cells, the peak respons e with the CIITA-transfected cells in fact occurring earlier (day 3 instead of day 5). Monoclonal antibodies to SLA-DR substantially inhibited the CD4 + T-cell responses in both cases. However, whereas the response to interfer on gamma-treated PIEC was partially inhibited by CTLA4-Ig, that to CIITA-tr ansfected PIEC was not. Conclusions, The strong stimulation of CD4+ T cells by the specific inducti on of MHC class II antigens demonstrates that PIEC cells constitutively exp ress functionally effective levels of costimulatory ligands. This finding s trengthens the case that vascular endothelial cells are professional antige n-presenting cells and that MHC class II-positive vascular endothelial cell s might play a role in the rejection of organ allografts.