ABSTRACT
Peripheral blood mononuclear cells (PBMC) from healthy donors and AML patients in remission were stimulated with phytohemagglutinin (PHA) and recombinant interleukin-2 (IL-2). These stimulated cells (lymphokine activated killer (LAK) cells) showed increased DNA synthesis as measured by 3H-Thymidine uptake. A synergistic effect of PHA and IL-2 was found. LAK cells' ability to kill acute myeloid leukemia (AML) blasts was investigated by the 51Cr release assay. LAK cells showed a cytotoxicity (over 10% specific 51Cr release) against 9/12 leukemic blasts, even at effector/target (E/T) ratios as low as 5:1. However, on average only 22.2% (SD 11.8) and 36.5% (SD 12.5) 51Cr release were obtained in 4- and 18-hour cytotoxicity assays, respectively, at an E/T ratio of 20:1. Leukemic blasts in 3/12 AML cases and normal PBMC were entirely resistant to lysis, even at an E/T ratio of 80:1. Susceptibility to lysis was not correlated to peanut-agglutinin receptor expression. LAK cells were more cytotoxic towards the K-562 cell line (natural killer activity) than unstimulated PBMC.
Subject(s)
Killer Cells, Natural/immunology , Leukemia, Myeloid, Acute/immunology , Cell Line , Cytotoxicity, Immunologic , Humans , Interleukin-2/pharmacology , Lymphocyte Activation , Recombinant Proteins/pharmacologyABSTRACT
Peripheral blood mononuclear cells (PBMC) from patients with acute myeloid leukemia (AML) or non-Hodgkin lymphoma (NHL) and healthy controls were stimulated with phytohemagglutinin (PHA) and interleukin-2 (IL-2). PHA (1 microgram/ml) induced higher 3H-thymidine incorporation than 800 U/ml IL-2 in PBMC from both controls and patients with AML in complete remission. A synergistic effect between PHA and IL-2 was found. Malignant B cells from 5/12 NHL expressed IL-2 receptors and showed proliferative response to IL-2, but not to PHA. PHA induced higher cytotoxicity toward AML blasts in lymphocytes from healthy controls than did IL-2. In addition, PHA induced higher cytotoxicity in lymphocytes from healthy controls than in those from patients with AML in remission. In contrast, no difference in cytotoxicity between controls' and patients' lymphocytes was found after stimulation with IL-2. No HLA restriction could be demonstrated. Normal peripheral blood mononuclear cells and leukemic blasts from 2/12 AML were completely resistant to cytotoxic cells even at effector:target ratios four times as high as those otherwise required.
Subject(s)
B-Lymphocytes/drug effects , Interleukin-2/pharmacology , Leukemia, Myeloid, Acute/blood , Lymphoma, Non-Hodgkin/blood , Phytohemagglutinins/pharmacology , T-Lymphocytes/drug effects , Cells, Cultured , Humans , Time FactorsABSTRACT
In a case of prolymphocytic leukemia (PLL), receptors for interleukin-2 (IL-2R) were demonstrated by immunofluorescence with a monoclonal antibody against IL-2R. Highly purified leukemic B-cells, cultured in vitro with recombinant IL-2 (r-IL-2), responded to IL-2 with a marked increase of DNA-synthesis. Both spontaneous and r-IL-2-induced proliferation of leukemic cells were totally abrogated by the anti-IL-2R monoclonal antibody.
Subject(s)
B-Lymphocytes/pathology , Interleukin-2/pharmacology , Leukemia, Lymphoid/pathology , Aged , Antibodies, Monoclonal , B-Lymphocytes/drug effects , Cell Division/drug effects , Cells, Cultured , DNA/biosynthesis , Humans , Immunologic Techniques , Male , Phenotype , Recombinant Proteins/pharmacologyABSTRACT
Cyclosporine A (CyA) treatment of 4 patients with severe aplastic anemia, who were ineligible for bone marrow transplantation, was carried out for periods of between 12 weeks to 20 months. A normalization of Hb and bone marrow, together with a marked improvement in WBC and platelet counts, were observed in only one of these four patients. The remission was maintained for 20 months under continuous treatment. A relapse occurred only when the patient himself interrupted treatment. No serious side effects were observed with CyA doses of 4-10 mg/kg/daily and blood concentrations of 200-400 ng/ml. No significant changes in T helper/T suppressor ratios were noted during the course of CyA treatment.
Subject(s)
Anemia, Aplastic/drug therapy , Cyclosporins/therapeutic use , Anemia, Aplastic/pathology , Cyclosporins/adverse effects , Humans , T-Lymphocytes/classification , T-Lymphocytes/pathology , T-Lymphocytes, Helper-Inducer/pathology , T-Lymphocytes, Regulatory/pathologyABSTRACT
Interleukin-2 (IL-2) for a long time has been considered as a T-cell specific growth factor which acts through distinct surface receptors present on activated, but not on resting, T-lymphocytes. Recently it has been shown that activated murine and human B-cells also express IL-2 receptors and respond to IL-2 with an increase of DNA synthesis. Some human B-cell malignancies have been reported to react with anti-IL-2 receptor antibodies, but no response to IL-2 has been documented in these cases. Here, in five of 11 B-cell leukemia/lymphoma cases, we identified cells which not only express the IL-2 receptor, but also respond to IL-2 stimulation, as shown by a marked increase of 3H-thymidine incorporation and by differentiation of lymphoma cells. The IL-2-induced 3H-thymidine uptake was completely blocked by a monoclonal antibody to IL-2 receptor, which indicates that IL-2 acted directly through functional IL-2 receptors.
