title: 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.
abstract: 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.
authors.affiliation: Department of Hematology, University Medical Center, Leiden, The Netherlands.
authors.forename: L M
authors.initials: LM
authors.lastname: Faber
authors.forename: J
authors.initials: J
authors.lastname: van der Hoeven
authors.forename: E
authors.initials: E
authors.lastname: Goulmy
authors.forename: A L
authors.initials: AL
authors.lastname: Hooftman-den Otter
authors.forename: S A
authors.initials: SA
authors.lastname: van Luxemburg-Heijs
authors.forename: R
authors.initials: R
authors.lastname: Willemze
authors.forename: J H
authors.initials: JH
authors.lastname: Falkenburg
mesh_terms: D000208:Acute Disease; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology*; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006648:Histocompatibility; D006801:Humans; D007951:Leukemia, Myeloid / Q000276:immunology* / Q000473:pathology; D015466:Leukemia, Myeloid, Chronic-Phase / Q000276:immunology / Q000473:pathology; D008297:Male; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D014411:Neoplastic Stem Cells / Q000276:immunology*; D012074:Remission Induction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014019:Tissue Donors; D014410:Tumor Stem Cell Assay
chemical_list: D006680:HLA Antigens; D015778:Minor Histocompatibility Antigens