STABLE CLONAL EXPANSION OF T-CELLS INDUCED BY BONE-MARROW TRANSPLANTATION

The immune mechanisms of T cells regeneration after bone marrow transp lantation (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, us ing reverse transcription polymerase chain reaction with T-cell recept or (TCR) V beta gene segment-specific primers and single-strand confor mation polymorphism. PBLs from patients and donors showed a heterogene ous 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, withou t a restriction of TCR V beta gene usage. Although part of the expansi on was transient, the majority was repeatedly detected even several mo nths later. Our results suggested that certain in vivo mechanisms main tain a stable clonal expansion of distinct T cells in marrow recipient s. We also found in a single patient with graft-versus-host disease a replacement of expanded clones by other clones during follow-up. Dimin ishing numbers of accumulation clones were found in long-term marrow r ecipients, indicating a general tendency for clonal expansion to subsi de progressively. Considered together, our data suggest the involvemen t of clonally expanded T cells in lymphoid regeneration and in acute a nd chronic immune responses after BMT. (C) 1996 by The American Societ y of Hematology.