RECOGNITION OF CLONOGENIC LEUKEMIC-CELLS, REMISSION BONE-MARROW AND HLA-IDENTICAL DONOR BONE-MARROW BY CD8+ OR CD4+ MINOR HISTOCOMPATIBILITY ANTIGEN-SPECIFIC CYTOTOXIC T-LYMPHOCYTES

被引:67
作者
FABER, LM
VANDERHOEVEN, J
GOULMY, E
OTTER, ALH
VANLUXEMBURGHEIJS, SAP
WILLEMZE, R
FALKENBURG, JHF
机构
[1] LEIDEN UNIV,MED CTR,DEPT HEMATOL,EXPTL HEMATOL LAB,2333 AA LEIDEN,NETHERLANDS
[2] LEIDEN UNIV,MED CTR,DEPT IMMUNOHEMATOL,2333 AA LEIDEN,NETHERLANDS
[3] LEIDEN UNIV,MED CTR,BLOOD BANK,2333 AA LEIDEN,NETHERLANDS
关键词
LEUKEMIA; CLONOGENIC (LEUKEMIC) HEMATOPOIETIC PROGENITOR CELLS; DIFFERENTIAL RECOGNITION; GRAFT-VERSUS-HOST DISEASE; GRAFT-VERSUS-LEUKEMIA REACTIVITY;
D O I
10.1172/JCI118134
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
We investigated whether minor histocompatibility (mH) antigen-specific cytotoxic T lymphocytes (CTL) can discriminate between leukemic hematopoietic progenitor cells (leukemic-HPC) from AML or CML patients, the HPC from their remission bone marrow (remission-HPC), and normal HPC from their HLA-identical sibling bone marrow donor (donor-HPC). Specific lysis by CD8+ CTL clones was observed not only of the leukemic-HPC but also of the donor-HPC in 3/4 patient/donor combinations expressing mH antigen HA-1, 3/5 combinations expressing mH antigen HA-2, 2/3 combinations expressing mH antigen HA-3, and 2/2 combinations expressing mH antigen HY-A1, In four patient/donor combinations the recognition of the donor-HPC was clearly less than of the leukemic-HPC, indicating differential susceptibility to lysis by these mH CTL clones, In addition, differential recognition of leukemic-HPC and remission-HPC within seven patients was analyzed. In one patient expressing the HA-2 antigen on the leukemic cells the recognition of the remission-HPC was clearly less than of the leukemic-HPC. One CD4(+) CTL clone showed specific lysis of the leukemic-HPC from an AML patient and a CML patient as well as of normal remission-HPC and donor-HPC, These results illustrate that in general CD8+ and CD4+ mH antigen specific CTL clones do not differentially recognize leukemic-HPC and normal-HPC, However, differences in susceptibility to lysis of malignant versus normal cells may contribute to a differential GVL effect.
引用
收藏
页码:877 / 883
页数:7
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