Summary
Transplantation involves preoperative ischemic periods that contribute to endothelial cell (EC) dysfunction and T‐cell activation, leading to graft rejection. As hypoxia is a major constituent of ischemia, we evaluated its effect on the ability of ECs to express HLA‐DR, which is required for presentation of antigens to T cells, and by itself serves as an important target for allogeneic T cells. Primary human umbilical vein ECs (HUVEC) and the human endothelial cell line EaHy926 were incubated in normoxia or hypoxia (PO2 < 0.3%). Hypoxia increased the membranal expression (by 4–6 fold, P < 0.01) and secretion (by sixfold, P < 0.05) of HLA‐DR protein, without influencing the accumulation of its mRNA. Alternative splicing, attenuated trafficking, or shedding from the plasma membrane were not observed, but the lysosomal inhibitor bafilomycin A1 reduced HLA‐DR secretion. Hypoxia‐induced endothelial HLA‐DR elevated and diminished the secretion of IL‐2 and IL‐10, respectively, from co‐cultured allogeneic CD4+ T cells in a HLA‐DR‐dependent manner, as demonstrated by the use of monoclonal anti‐HLA‐DR. Our results indicate a yet not fully understood post‐translational mechanism(s), which elevate both membranal and soluble HLA‐DR expression. This elevation is involved in allogeneic T‐cell activation, highlighting the pivotal role of ECs in ischemia/hypoxia‐associated injury and graft rejection.