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

Transfusion-associated graft-versus-host disease (TA-GVHD) is usually a fat al outcome of blood transfusion therapy, caused by viable leucocytes contai ned in the donor blood. Most cases of TA-GVHD occur when less than 4-d-old brood is transfused. We therefore examined the molecular changes that occur during storage that may account for the paucity of TA-GVHD following infus ion of older blood. Leucocyte number and viability were essentially unchang ed from freshly obtained brood, but the expression of cell-surface lymphocy te 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 b y d 9 of storage at 4 degreesC. The decrease in CD antigen expression direc tly correlated with a decreasing ability to induce activation of the T-lymp hocyte cellular signal transduction pathway As a result, cells became less responsive in a mixed lymphocyte culture(MLC) by d 3, with abrogation of th e MLC responsiveness by d 5, Donor leucocytes stored for 4 d or less at 4 d egreesC were able to partially re-express CD antigens and reconstitute thei r signalling pathway when placed at 37 degreesC, whereas those stored for m ore than 4 d were not. These irreversible changes result from a permanent d ownregulation of donor cell protein synthesis. These findings provide a mec hanism to explain the paucity of TA-GVHD following transfusion of blood tha t is more than 4 d-old. Further study may show that aged blood provides add itional assurances for the prevention of TA-GVHD; however, use of aged bloo d should not replace current protocols using irradiation.