Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8737629 | Human Immunology | 2018 | 9 Pages |
Abstract
This review focuses on mechanistic studies performed in recipients of non-myeloablative bone marrow transplant regimens developed at Massachusetts General Hospital in HLA-identical and HLA-mismatched haploidentical combinations, initially as a platform for treatment of hematologic malignancies with immunotherapy in the form of donor leukocyte infusions, and later in combination with donor kidney transplantation for the induction of allograft tolerance. In patients with permanent mixed chimerism, central deletion may be a major mechanism of long-term tolerance. In patients in whom donor chimerism is only transient, the kidney itself plays a significant role in maintaining long-term tolerance. A high throughput sequencing approach to identifying and tracking a significant portion of the alloreactive T cell receptor repertoire has demonstrated biological significance in transplant patients and has been useful in pointing to clonal deletion as a long-term tolerance mechanism in recipients of HLA-mismatched combined kidney and bone marrow transplants with only transient chimerism.
Keywords
MLRGVLTCrMiHACMLGvHDAPCBMTTregTBIDLIMinor histocompatibility antigenantigen-presenting cellTotal body irradiationgraft-vs-host diseaseLDAClonal deletionAllograft rejectionRegulatory T cellRegulatory T cellscell-mediated lympholysislimiting dilution analysismixed lymphocyte reactionBone marrow transplantationMixed chimerismT cell receptor
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Authors
Megan Sykes,