Generation of leukemia-reactive cytotoxic T lymphocytes from HLA-identical donors of patients with chronic myeloid leukemia using modifications of a limiting dilution assay

被引:26
作者
Smit, WM [1 ]
Rijnbeek, M [1 ]
van Bergen, CAM [1 ]
Willemze, R [1 ]
Falkenburg, JHF [1 ]
机构
[1] Leiden Univ, Med Ctr, Dept Hematol, Lab Expt Hematol, NL-2300 RC Leiden, Netherlands
关键词
cytotoxic T lymphocytes; chronic myeloid leukemia; limiting dilution assay; host-reactive;
D O I
10.1038/sj.bmt.1701135
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
Donor leukocyte transfusions (DLT) have an anti-leukemic effect in most patients with a relapse of chronic myeloid leukemia (CML) after allogeneic stem cell transplantation. However, DLT are often complicated by graft-versus-host disease, Selection of donor lymphocytes with a relative specificity for leukemic cells is desirable, The generation of leukemia-reactive cytotoxic T lymphocyte (CTL) responses between HLA-identical donors and patients in bulk cultures showed major variations, and false negative results were observed, In a modification of a limiting dilution analysis (LDA) two-fold serial dilutions of HLA-identical donor mononuclear cells (MNC) were cultured in the presence of CML cells, The anti-leukemic CTL precursor frequencies in these donors varied between <1 and 9 per 10(6) MNC, KLA-restricted CD4(+) or CD8(+) lymphocytes as well as MHC non-restricted gamma delta T cells were responsible for the anti-leukemic responses, A positive correlation between cytotoxicity in the various wells after 3, 4 and 5 weeks of culture could be found, The LDA may be superior to bulk cultures in selecting stable immune responses and in separating multiple different antileukemic T cell responses in each donor-patient combination.
引用
收藏
页码:553 / 560
页数:8
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