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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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Submitted March 18, 2008
Accepted May 24, 2008
Overlap between in vitro donor anti-host and in vivo post-transplantation TCR V utilization: A new paradigm for designer allogeneic blood and marrow transplantation
Thea M. Friedman*, Kira Goldgirsh, Stephanie A. Berger, Jenny Zilberberg, Joanne Filicko-O'Hara, Neal Flomenberg, Michele Donato, Scott D. Rowley, and Robert Korngold
Cancer Center, Hackensack University Medical Center, Hackensack, New Jersey, United States
Hematologic Malignancies, Blood and Marrow Transplant Program; Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, United States
Touro University College of Medicine, Hackensack, New Jersey, United States
* Corresponding author; email: tfriedman{at}humed.com.
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 V 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 (PBL) with those detected in vivo post-transplantation. The results indicated that for most V families that exhibited alloreactive CDR3-size skewing, there was a robust overlap between the in vitro anti-patient 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 V family-depletion for designer transplants to improve outcomes.

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