Overlap between in vitro donor antihost and in vivo posttransplantation TCR Vβ use: a new paradigm for designer allogeneic blood and marrow transplantation
Autor: | Robert Korngold, Michele L. Donato, Jenny Zilberberg, Neal Flomenberg, Thea M. Friedman, Scott D. Rowley, Joanne Filicko-O'Hara, Stephanie A. Berger, Kira Goldgirsh |
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Rok vydání: | 2008 |
Předmět: |
Adult
Male medicine.medical_specialty Receptors Antigen T-Cell alpha-beta T-Lymphocytes Immunology Graft vs Host Disease chemical and pharmacologic phenomena Bone Marrow Cells Complementarity determining region Biology Biochemistry In vivo Internal medicine Inside Blood medicine Humans Transplantation Homologous Aged Bone Marrow Transplantation Transplantation Hematology Marrow transplantation T-cell receptor Cell Biology Middle Aged Complementarity Determining Regions humanities In vitro Treatment Outcome surgical procedures operative medicine.anatomical_structure Hematologic Neoplasms Female Bone marrow Stem cell |
Zdroj: | Blood. 112:3517-3525 |
ISSN: | 1528-0020 0006-4971 |
DOI: | 10.1182/blood-2008-03-145391 |
Popis: | Following allogeneic blood and marrow transplantation (BMT), mature donor T cells can enhance engraftment, counteract opportunistic infections, and mount graft-versus-tumor (GVT) responses, but at the risk of developing graft-versus-host disease (GVHD). With the aim of separating the beneficial effects of donor T cells from GVHD, one approach would be to selectively deplete subsets of alloreactive T cells in the hematopoietic cell inoculum. In this regard, TCR Vβ repertoire analysis by CDR3-size spectratyping can be a powerful tool for the characterization of alloreactive T-cell responses. We investigated the potential of this spectratype approach by comparing the donor T-cell alloresponses generated in vitro against patient peripheral blood lymphocytes (PBLs) with those detected in vivo posttransplantation. The results indicated that for most Vβ families that exhibited alloreactive CDR3-size skewing, there was a robust overlap between the in vitro antipatient and in vivo spectratype histograms. Thus, in vitro spectratype analysis may be useful for determining the alloreactive T-cell response involved in GVHD development and, thereby, could serve to guide select Vβ family depletion for designer transplants to improve outcomes. |
Databáze: | OpenAIRE |
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