Persistence of clonal T-cell expansions following high-dose chemotherapy and autologous peripheral blood progenitor cell rescue

Abstract

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.

B- and T-lymphocyte number and function in HIV+/HIV− lymphoma patients treated with high-dose chemotherapy and autologous bone marrow transplantation

“…However, we could also demonstrate relevant therapy-induced modifications of TCRBV chain profiles, including enlargement in TCR heterogeneity of T cells expressing certain TCRBV, and contraction in diversity of cells bearing other TCRBV, as well as disappearance of some clonal expansions and appearance of others. Therefore, our data differ from those reporting that patients undergoing ASCT after HDC regenerate clonal expansions consistent with those found in the pre-treatment period37. Furthermore, these modifications could be different in HIV + and HIV − patients as shown by unsupervised hierarchical clustering discriminating between the two groups.…”

Antigen‐Specific T‐Cell Immunity in Multiple Myeloma Patients is Restored Following High‐Dose Therapy: Implications for Timing of Vaccination

“…Additionally, expansion of mature specific T cells is taking place particularly in the CD4 + subset, which generally exhibited increased cytokine and proliferation response even without Ag re‐stimulation. In accordance with these findings, both clonal T‐cell expansion and regeneration of T‐cell receptor repertoire have been demonstrated after HD and stem cell transplantation by use of T‐cell receptor analyses [32].…”

Interleukin-7 deficiency in rheumatoid arthritis: consequences for therapy-induced lymphopenia

“…Control patients (Table 2) included five individuals with lung carcinoma, one with breast carcinoma and one with melanoma. They received unmanipulated autologous grafts following high-dose chemotherapy, as previously documented [32]. For the IL-7 longitudinal studies, we analyzed four lymphoma and three sarcoma patients.…”