Persistence of clonal T-cell expansions following high-dose chemotherapy and autologous peripheral blood progenitor cell rescue.
Analysing the regeneration of T lymphocytes after high-dose chemotherapy with autologous peripheral blood progenitor cell rescue (PBPCR) may help elucidate the mechanisms of immune recovery. The T-cell receptor variable beta chain (TCRBV) repertoire of adult patients undergoing high-dose chemotherapy was analysed by flow cytometry, before and after treatment. Four patients were found to have a stable expansion present (TCRBV3, 17, 21 and 22) ranging from 8% to 42% of the CD4(+) or CD8(+) repertoire. We demonstrated that, in these patients, following high-dose chemotherapy and autologous stem cell transplantation, the clonal expansions reappeared in peripheral blood and returned to pretransplant levels. Three expansions (CD3(+)CD8(+)TCRBV3(+), CD3(+)CD4(+)TCRBV21(+) and CD3(+)CD8(+)TCRBV22(+)) were further defined by sequence analysis of the complementarity-determining region (CDR)3 portion within the TCR rearrangements. These were shown to be predominantly clonal, with the same sequences being identified in peripheral blood before and after PBPCR, providing evidence that the overwhelming majority of T cells in these expansions arise from mature lymphocytes. This study demonstrated that patients undergoing autologous PBPCR for high-dose chemotherapy regenerate clonal expansions, consistent with pretreatment levels. They also regenerate T-cell repertoires with each TCRBV family represented to a similar level as that prior to high-dose chemotherapy.
Protheroe
A S
AS
Imperial Cancer Research Fund Cancer Medicine Research Unit, St James's University Hospital, Leeds, UK. csjap@cancermed.leeds.ac.uk
Pickard
C
C
Johnson
P W
PW
Craddock
T
T
Shefta
J
J
Short
K
K
Lancaster
F
F
Selby
P J
PJ
Henwood
J
J
Boylston
A W
AW
D000595:Amino Acid Sequence; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D016465:Bone Marrow Purging; D001943:Breast Neoplasms / Q000276:immunology / Q000601:surgery; D018288:Carcinoma, Small Cell / Q000276:immunology / Q000601:surgery; D002330:Carmustine / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D005434:Flow Cytometry; D019085:Fluorescent Antibody Technique, Direct; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D018237:Germinoma / Q000276:immunology / Q000601:surgery; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology / Q000601:surgery; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology / Q000601:surgery; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000601:surgery; D008875:Middle Aged; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000276:immunology / Q000601:surgery; D016133:Polymerase Chain Reaction / Q000379:methods; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D014182:Transplantation, Autologous
D018906:Antineoplastic Agents, Alkylating; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D003520:Cyclophosphamide; D002330:Carmustine