Overlap between in vitro donor antihost and in vivo posttransplantation TCR Vbeta use: a new paradigm for designer allogeneic blood and marrow transplantation.
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 Vbeta 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 Vbeta 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 Vbeta family depletion for designer transplants to improve outcomes.
Friedman
Thea M
TM
Cancer Center, Hackensack University Medical Center, NJ, USA. tfriedman@humed.com
Goldgirsh
Kira
K
Berger
Stephanie A
SA
Zilberberg
Jenny
J
Filicko-O'Hara
Joanne
J
Flomenberg
Neal
N
Donato
Michele
M
Rowley
Scott D
SD
Korngold
Robert
R
D000328:Adult; D000368:Aged; D001854:Bone Marrow Cells / Q000166:cytology; D016026:Bone Marrow Transplantation / Q000295:instrumentation / Q000379:methods*; D022801:Complementarity Determining Regions / Q000096:biosynthesis; D005260:Female; D006086:Graft vs Host Disease; D019337:Hematologic Neoplasms / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism* / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000378:metabolism; D014184:Transplantation, Homologous / Q000295:instrumentation / Q000379:methods*; D016896:Treatment Outcome
D022801:Complementarity Determining Regions; D016693:Receptors, Antigen, T-Cell, alpha-beta