title: 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 degrees 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 degrees C were able to partially re-express CD antigens and reconstitute their signalling pathway when placed at 37 degrees 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.
authors.affiliation: Department of Medicine, University of Toronto, Ontario, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Chang
authors.forename: M
authors.initials: M
authors.lastname: Voralia
authors.forename: M
authors.initials: M
authors.lastname: Bali
authors.forename: G D
authors.initials: GD
authors.lastname: Sher
authors.forename: D R
authors.initials: DR
authors.lastname: Branch
mesh_terms: D015415:Biomarkers / Q000032:analysis; D001793:Blood Preservation; D018801:CD2 Antigens / Q000032:analysis; D018106:CD28 Antigens / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D015925:Cryopreservation; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D014176:Protein Biosynthesis; D015375:Receptors, Interleukin-2 / Q000032:analysis; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D013997:Time Factors
chemical_list: D015415:Biomarkers; D018801:CD2 Antigens; D018106:CD28 Antigens; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D015375:Receptors, Interleukin-2; D017493:Leukocyte Common Antigens