Stable clonal expansion of T cells induced by bone marrow transplantation.
The immune mechanisms of T cells regeneration after bone marrow transplantation (BMT) and the factors maintaining allogeneic marrow graft in the host are still unknown. To pursue this issue, we analyzed T-cell clonality of peripheral blood lymphocytes (PBLs) in BMT recipients, using reverse transcription polymerase chain reaction with T-cell receptor (TCR) V beta gene segment-specific primers and single-strand conformation polymorphism. PBLs from patients and donors showed a heterogeneous T-cell population with oligoclonal accumulations of CD8+ T cells. When PBLs were cultured in HLA-matched mixed lymphocytes reaction in vitro, no distinct clonal expansion was observed. However, after BMT, oligoclonal expansions were induced in the recipients in vivo, without a restriction of TCR V beta gene usage. Although part of the expansion was transient, the majority was repeatedly detected even several months later. Our results suggested that certain in vivo mechanisms maintain a stable clonal expansion of distinct T cells in marrow recipients. We also found in a single patient with graft-versus-host disease a replacement of expanded clones by other clones during follow-up. Diminishing numbers of accumulation clones were found in long-term marrow recipients, indicating a general tendency for clonal expansion to subside progressively. Considered together, our data suggest the involvement of clonally expanded T cells in lymphoid regeneration and in acute and chronic immune responses after BMT.
Masuko
K
K
Division of Rheumatology and Molecular Immunology, St. Marianne University, Kanagawa, Japan.
Kato
S
S
Hagihara
M
M
Tsuchida
F
F
Takemoto
Y
Y
Izawa
K
K
Kato
T
T
Yamamori
S
S
Mizushima
Y
Y
Nishioka
K
K
Tsuji
K
K
Yamamoto
K
K
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002455:Cell Division; D002648:Child; D002675:Child, Preschool; D002999:Clone Cells / Q000166:cytology; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology; D006801:Humans; D007223:Infant; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000166:cytology*
D016693:Receptors, Antigen, T-Cell, alpha-beta