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.
Cancer Center, Hackensack University Medical Center, NJ, USA. tfriedman@humed.com
Thea M
TM
Friedman
Kira
K
Goldgirsh
Stephanie A
SA
Berger
Jenny
J
Zilberberg
Joanne
J
Filicko-O'Hara
Neal
N
Flomenberg
Michele
M
Donato
Scott D
SD
Rowley
Robert
R
Korngold
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