Mechanisms of Alloimmunization and Subsequent Bone Marrow Transplantation Rejection Induced by Platelet Transfusion in a Murine Model

• Type of Material: Article
• Authors: Seema R Patel, Emory University; Nicole H Smith, Emory University; Linda Kapp, Emory University; James Zimring, Emory University
• Language: English
• Date: 2012-05-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.
• Final Published Version (URL): http://dx.doi.org/10.1111/j.1600-6143.2011.03959.x
• Title of Journal or Parent Work: American Journal of Transplantation
• ISSN: 1600-6135
• Volume: 12
• Issue: 5
• Start Page: 1102
• End Page: 1112
• Grant/Funding Information: These studies were supported in part by NIH grant R01HL092977.
• Keywords: Science & Technology; transfusion; GRAFT-REJECTION; SEVERE APLASTIC-ANEMIA; Transplantation; CD8 T-CELLS; Life Sciences & Biomedicine; ENGRAFTMENT; STEM-CELL TRANSPLANTATION; RECIPIENTS; T cells; minor antigens; DISEASE; FLUDARABINE; THALASSEMIA; platelet; Surgery; RISK-FACTORS; Bone marrow transplantation
• Research Categories: Health Sciences, Pathology; Health Sciences, Medicine and Surgery

Abstract

For many nonmalignant hematological disorders, HLA-matched bone marrow transplantation (BMT) is curative. However, due to lack of neoplasia, the toxicity of stringent conditioning regimens is difficult to justify, and reduced intensity conditioning is used. Unfortunately, current reduced intensity regimens have high rates of BMT rejection. We have recently reported in a murine model that mHAs on transfused platelet products induce subsequent BMT rejection. Most nonmalignant hematological disorders require transfusion support prior to BMT and the rate of BMT rejection in humans correlates with the number of transfusions given. Herein, we perform a mechanistic analysis of platelet transfusion-induced BMT rejection and report that unlike exposure to alloantigens during transplantation, platelet transfusion primes alloimmunity but does not stimulate full effector function. Subsequent BMT is itself an additional and distinct immunizing event, which does not induce rejection without antecedent priming from transfusion. Both CD4 + and CD8 + T cells are required for priming during platelet transfusion, but only CD8 + T cells are required for BMT rejection. In neither case are antibodies required for rejection to occur. This article demonstrates the roles of CD4 + and CD8 + T cells and antibodies in the process of platelet transfusioninduced bone marrow transplant rejection across minor antigen barriers for MHC identical donors and recipients.