Lymphoid reconstitution after autologous PBSC transplantation with FACS-sorted CD34+ hematopoietic progenitors.
T-cell and B-cell reconstitution was studied in nine patients who received fluorescence activated cell sorter (FACS)-sorted autologous CD34+ hematopoietic progenitor cells (HPC). The mean numbers of T cells (CD3+), B cells (CD19+) and CD34+ HPC administered to each patient were .004, .002, and 1.8 x 10(6) cells/kg, respectively. After high-dose myeloablative chemotherapy (busulfan, cyclophosphamide, etoposide) CD34+) HPC were infused and lymphoid reconstitution was monitored using flow cytometry and reverse transcriptase-polymerase chain reaction (RT-PCR) amplification of VDJ T-cell receptor (TcR) sequences. Restoration of normal numbers of peripheral blood T cells and B cells among recipients of FACS-sorted CD34+ HPC was delayed compared to recipients of non-T-cell-depleted PBSC autografts. In both patient groups, the circulating T cells were primarily CD4-, CD8+, alphabeta TcR+, and CD45RO+, CD45RA- during the first 2 months after transplant. Subsequent increases in the frequency of CD45RA+ CD45RO- T cells occurred at 2 to 3 months after transplant, suggesting maturation of CD34+ hematopoietic progenitors to "naive" T cells. Analysis of the TcR repertoire after hematopoietic reconstitution demonstrated decreased diversity of Vbeta TcR expression associated with global decreases in the absolute number of total peripheral blood T cells and most Vbeta TcR+ subsets. Three of nine recipients of FACS-sorted CD34+ HPC demonstrated significant increases in the percentage of gammadelta+ peripheral T cells and CD5+ B cells at 3 to 9 weeks after transplantation, and all patients had transient oligoclonal expansions of T cells expressing specific Vbeta TcR. Transplantation with highly purified CD34+ HPC results in reduced diversity of the peripheral T-cell repertoire during the early post-transplant period compared with patients receiving unmanipulated or MoAb-depleted transplants.
Bomberger
C
C
Stem Cell Biology Program, Emory University, Atlanta, GA 30322, USA.
Singh-Jairam
M
M
Rodey
G
G
Guerriero
A
A
Yeager
A M
AM
Fleming
W H
WH
Holland
H K
HK
Waller
E K
EK
D000328:Adult; D018952:Antigens, CD34; D001402:B-Lymphocytes / Q000473:pathology; D002454:Cell Differentiation; D002469:Cell Separation / Q000379:methods; D005434:Flow Cytometry; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy*; D008875:Middle Aged; D013601:T-Lymphocytes / Q000473:pathology; D014182:Transplantation, Autologous
D018952:Antigens, CD34