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 immun...

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Bibliographic Details
Published in:Blood 2006-01, Vol.107 (1), p.187-189
Main Authors: Zimring, James C., Hair, Gregory A., Deshpande, Seema S., Horan, John T.
Format: Article
Language:English
Subjects:
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Animals
Biological and medical sciences
Bone Marrow Transplantation - adverse effects
Bone Marrow Transplantation - immunology
Bone marrow, stem cells transplantation. Graft versus host reaction
CD8-Positive T-Lymphocytes - immunology
Chickens
Cross-Priming
Erythrocyte Transfusion
Erythrocytes - immunology
Graft Rejection - etiology
Graft Rejection - immunology
Histocompatibility Antigens Class I - immunology
Immunization
Leukocyte Reduction Procedures
Medical sciences
Mice
Minor Histocompatibility Antigens - immunology
Ovalbumin
Transfusions. Complications. Transfusion reactions. Cell and gene therapy
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Summary: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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2005-07-3059