Irreversible loss of donor blood leucocyte activation may explain a paucity of transfusion‐associated graft‐versus‐host disease from stored blood

Abstract

Transfusion‐associated graft‐versus‐host disease (TA‐GVHD) is usually a fatal outcome of blood transfusion therapy, caused by viable leucocytes contained in the donor blood. Most cases of TA‐GVHD occur when less than 4‐d‐old blood is transfused. We therefore examined the molecular changes that occur during storage that may account for the paucity of TA‐GVHD following infusion of older blood. Leucocyte number and viability were essentially unchanged from freshly obtained blood, but the expression of cell‐surface lymphocyte activation antigens (CD3, CD4, CD28, CD2, CD45) decreased rapidly within the first 24 h and continued to fall to less than 20% of original levels by d 9 of storage at 4°C. The decrease in CD antigen expression directly correlated with a decreasing ability to induce activation of the T‐lymphocyte cellular signal transduction pathway. As a result, cells became less responsive in a mixed lymphocyte culture (MLC) by d 3, with abrogation of the MLC responsiveness by d 5. Donor leucocytes stored for 4 d or less at 4°C were able to partially re‐express CD antigens and reconstitute their signalling pathway when placed at 37°C, whereas those stored for more than 4 d were not. These irreversible changes result from a permanent downregulation of donor cell protein synthesis. These findings provide a mechanism to explain the paucity of TA‐GVHD following transfusion of blood that is more than 4 d‐old. Further study may show that aged blood provides additional assurances for the prevention of TA‐GVHD; however, use of aged blood should not replace current protocols using irradiation.