Transfer of PR1-specific T-cell clones from donor to recipient by stem cell transplantation and association with GvL activity.
BACKGROUND
The curative effects of GvL following transfer of donor-derived T cells during allogeneic stem cell transplantation (SCT) are well established. However, little is known about the nature, origin and kinetics of the anti-leukemic T-cell responses involved.


METHODS
We used quantitative real-time PCR (qRT-PCR) for interferongamma mRNA production (IFN-gamma) and PR1/HLA-A*0201 tetramer staining to detect PR1-specific CD8+ T-cell activity in a donor and a patient with CML. Unbiased strand switch anchored RT-PCR was used to further characterize specific clones in PR1 sorted CD8+ T-cell populations.


RESULTS
We identified PR1-specific CD8(+) T-cell clones from a donor pre-transplant, and demonstrated their transfer in the recipient's blood post-SCT using molecular tracking of Ag-specific T-cell receptors. PR1-specific CD8(+) T-cell populations were polyclonal, with a range of functional avidities for cognate Ag, and displayed predominantly effector memory phenotype early post-SCT, suggesting active stimulation in vivo. Expansion of these PR1-specific CD8(+) T-cell clones in the recipient was followed by complete remission of CML.


CONCLUSIONS
This report represents the first direct demonstration that PR1-specific CD8(+) T-cell clones can be transferred during SCT, and supports the feasibility of pre-transplant vaccination strategies that aim to boost the number of anti-leukemic T cells in the graft.
Rezvani
K
K
Stem Cell Allotransplantation Section, Hematology Branch, National Heart Lung Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Rezvanik@nhlbi.nih.gov
Price
D A
DA
Brenchley
J M
JM
Kilical
Y
Y
Gostick
E
E
Sconocchia
G
G
Hansmann
K
K
Kurlander
R
R
Douek
D C
DC
Barrett
A J
AJ
D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000637:transplantation*; D005240:Feasibility Studies; D020544:Graft vs Leukemia Effect; D015234:HLA-A Antigens / Q000276:immunology*; D015789:HLA-A2 Antigen; D006801:Humans; D016130:Immunophenotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology* / Q000628:therapy; D008297:Male; D053146:Myeloblastin / Q000276:immunology*; D009842:Oligopeptides / Q000276:immunology; D033581:Stem Cell Transplantation
D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D009842:Oligopeptides; D053146:Myeloblastin