Immunization to minor histocompatibility antigens on transfused RBCs through crosspriming into recipient MHC class I pathways.
Increased rates of graft rejection after bone marrow transplantation (BMT) are observed in patients whose illnesses--such as sickle cell disease, thalassemia, and aplastic anemia--necessitate chronic transfusion before BMT. Because BM transplants in these patients are routinely HLA matched, any immunization responsible for increased rejection is likely against minor histocompatibility antigens (mHAs). It has been assumed that contaminating leukocytes in red blood cell (RBC) units are the main sources of immunization to mHAs. However, in this report, we demonstrate that antigens on donor RBCs are presented in the major histocompatibility complex (MHC) class I pathway of recipient antigen-presenting cells, resulting in activation and expansion of recipient CD8+ T cells specific for donor mHAs. Given that human hematopoietic progenitor cells express many of the known mHAs, this observation provides a mechanism by which chronic transfusion of even stringently leukoreduced RBCs may result in sufficient mHA immunization to increase the frequency of BMT rejection.
Zimring
James C
JC
Transfusion Medicine Program, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Woodruff Memorial Bldg, Ste 7301, 101 Woodruff Circle, Atlanta, GA 30322, USA. jzimrin@emory.edu
Hair
Gregory A
GA
Deshpande
Seema S
SS
Horan
John T
JT
D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002645:Chickens; D045142:Cross-Priming; D017707:Erythrocyte Transfusion; D004912:Erythrocytes / Q000276:immunology*; D006084:Graft Rejection / Q000209:etiology / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007114:Immunization; D047589:Leukocyte Reduction Procedures; D051379:Mice; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D010047:Ovalbumin
D015395:Histocompatibility Antigens Class I; D015778:Minor Histocompatibility Antigens; D010047:Ovalbumin