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 wi th autologous peripheral blood progenitor cell rescue (PBPCR) may help eluc idate the mechanisms of immune recovery. The T-cell receptor variable beta chain (TCRBV) repertoire of adult patients undergoing high-dose chemotherap y was analysed by flow cytometry, before and after treatment. Four patients were found to have a stable expansion present (TCRBV3, 17, 21 and 22) rang ing from 8% to 42% of the CD4(+) or CD8(+) repertoire. We demonstrated that , in these patients, following high-dose chemotherapy and autologous stem c ell transplantation, the clonal expansions reappeared in peripheral blood a nd 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 porti on within the TCR rearrangements. These were shown to be predominantly clon al, 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 regene rate clonal expansions, consistent with pretreatment levels. They also rege nerate T-cell repertoires with each TCRBV family represented to a similar l evel as that prior to high-dose chemotherapy.