T lymphocytes cultured from chronic myelogenous leukemia bone marrow suppress autologous hematopoietic progenitors.
In vitro culture of T lymphocytes infiltrating solid tumors has resulted in populations with significant, and sometimes selective, anti-tumor activity. In this study we evaluated the ability of T lymphocyte populations generated from the marrow of patients with chronic myelogenous leukemia (CML) to suppress autologous hematopoietic progenitors. T lymphocyte populations were obtained by culture of CML bone marrow mononuclear cells (BMMNC) with low dose rIL-2 (25 U/ml) after initial PHA stimulation, and restimulation during culture with autologous marrow cells. Preincubation of the cultured CML T lymphocytes in close contact with autologous BMMNC resulted in significant, dose-related suppression of autologous CFU-MIX and BFU-E colonies (P < 0.001). Close contact between effectors and targets was important for progenitor suppression. Progenitor suppression was mediated by CD4-positive T lymphocytes. In contrast to the significant suppression of autologous progenitors by CML T lymphocytes, T lymphocytes from normal bone marrow did not suppress autologous progenitors. We conclude that T lymphocyte populations with significant autologous progenitor suppressing ability can be generated from CML marrow. These observations may be of therapeutic value in CML.
Bhatia
R
R
Department of Medicine, University of Minnesota Medical School, University of Minnesota, Minneapolis 55455, USA.
McGlave
P B
PB
D015703:Antigens, CD / Q000032:analysis; D001853:Bone Marrow / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D006684:HLA-DR Antigens / Q000032:analysis; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007108:Immune Tolerance; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000494:pharmacology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology* / Q000473:pathology*; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology
D015703:Antigens, CD; D006684:HLA-DR Antigens; D007376:Interleukin-2; D011994:Recombinant Proteins