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
Rok vydání: 2008
Předmět:
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