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Blood, 15 October 2008, Vol. 112, No. 8, pp. 3517-3525.
Prepublished online as a Blood First Edition Paper on June 9, 2008; DOI 10.1182/blood-2008-03-145391.


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TRANSPLANTATION

Overlap between in vitro donor antihost and in vivo posttransplantation TCR Vβ use: a new paradigm for designer allogeneic blood and marrow transplantation

Thea M. Friedman1,2, Kira Goldgirsh1, Stephanie A. Berger1, Jenny Zilberberg1, Joanne Filicko-O'Hara3, Neal Flomenberg3, Michele Donato1, Scott D. Rowley1, and Robert Korngold1,2

1 Cancer Center, Hackensack University Medical Center, NJ; 2 Touro University College of Medicine, Hackensack, NJ; and 3 Hematologic Malignancies, Blood and Marrow Transplant Program, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA

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.


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