[NK cell activity in childhood leukemia].
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Biomedical subjects
Publications and source records attributed to T Akabane.
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The natural killer (NK) activity of circulating lymphocytes of 38 children with acute lymphoblastic leukemia (ALL) in complete remission was studied by 51Cr-release cytotoxicity assay. NK activity of the non-T-cell fraction (NKnon-T) and of the T-cell fraction (NKT) was also measured. In addition, the number of circulating NK cells was determined by an immunofluorescence technique using monoclonal anti-Leu-7 (HNK-1) antibody. Total NK activity of the ALL patients in complete remission was impaired during maintenance therapy (P less than 0.001) and after cessation of therapy (P less than 0.05). NK activity of NKnon-T and NKT cells was equally impaired (P less than 0.05). The numbers of Leu-7+ cells and NK activity units were decreased during maintenance therapy (P less than 0.05), but approached normal after cessation of therapy. These data indicate that decreased NK activity of childhood ALL in complete remission during maintenance therapy is due to a decrease in total NK cells and impaired function of both NKnon-T and NKT cells.
Cytostasis activity of mononuclear cells (MNC) was studied in 32 children with acute lymphoblastic leukemia (ALL) with special reference to the relapse of the disease. MNC from ALL even in complete remission had decreased cytostasis activity. The cytostasis activity in ALL patients who relapsed within 3 months after the assay was significantly lower than that of the patients who continued to be in remission for more than 6 months after the assay. Serial assays in six patients demonstrated that a sudden decrease of the cytostasis activity occurred 4 to 8 weeks before the relapse when there were no apparent changes of the peripheral blood cell counts and bone marrow pictures. When relapsed, the cytostasis activity was markedly impaired. These results demonstrate that the assay of MNC cytostasis activity is a useful tool to predict or detect relapse of ALL at an earlier time. The cytostasis activity was still decreased after the cessation of chemotherapy for ALL, demonstrating a characteristic immunologic defect in ALL.
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Leukemic cells from a child with acute lymphoblastic leukemia (ALL) had high natural killer (NK) activity against K562 as determined by the 51Cr release assay at a 40:1 effector:target ratio: percent lysis was 76.8% (147.4% of normal lymphocyte value) and higher than that of control leukemic cells from 12 childhood ALL (0.1% +/- 0.3%). Two leukemic cell lines (SPI-801 and SPI-802) were established from the patient, and they were essentially the same as the freshly harvested leukemic cells in their morphology, cytochemistry, immunologic markers, and functions. The cultured cell lines as well as the fresh leukemic cells had receptors for sheep red blood cells, IgG-Fc, and C3. The cultured cells were OKM1+, Ia+ and asialo-GM1+, and were OKT-3-, OKT-4-, OKT-6-, OKT-8-, Leu-7-, human monocyte-, common ALL-, T cell-, surface Ig-, and cytoplasmic IgM- as determined by the immunofluorescence method. The two cell lines shared the same chromosome abnormalities. Their chromosomes were in hypotriploid region (63--73), and 6q-, 11p+, and several marker chromosomes were demonstrated. They had spontaneous cytotoxicity against K562 (percent lysis: up to 17.8% and 33.5% of normal lymphocyte value in SPI-801 and SPI-802, respectively) and Molt-3 (38.2% and 27.8% of normal lymphocyte value), but not against Raji and mitogen-induced normal lymphoblasts. Such phenotypic and functional characteristics of the fresh leukemic cells and cultured cells are virtually identical to those of NK cells, demonstrating a new phenotype of childhood ALL of NK cell origin.
T lymphocytotoxic human fetal antibody- (TLFA) containing cord IgM (TLFA IgM) was purified from cord blood. The proliferation of maternal mixed lymphocyte culture-(MLC) induced and long-term cultured T cells (LCT) specific to the paternal non-T cells in the presence of interleukin 2 (IL 2) was inhibited by treatment with the respective TLFA IgM plus complement (C). Sixty-six to 78% of Leu-2a-positive maternal LCT were stained with the respective TLFA IgM, as determined by anti-Leu antibodies and TLFA IgM double-staining. Moreover, TLFA IgM plus C treatment reduced the killer activity of the respective maternal LCT against the PHA-induced paternal target cells. Therefore, TLFA-positive killer T cells of maternal LCT belong to certain killer T cell subsets of Leu-2a-positive pan-killer T cells, and TLFA contains a potential antibody against maternal killer T cells.
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A 7-year-old boy with acute monocytic leukemia (AMoL) had leukemic monocytes that formed spontaneous rosettes with sheep red blood cells (E-rosette). The E-rosette formation was observed in 75% of leukemic monocytes at 4 C and in 37% at 37 C. Cytochemical and ultrastructural studies confirmed that the rosette-forming cells were leukemic monocytes. The leukemic monocytes attached to the red blood cells at a portion of their surface and did not show any phagocytic processes at the electron microscopic level. The data from this patient seem to indicate that in a rare case of AMoL, abnormal myeloid lymphoid stem cells can differentiate to monocytes while retaining lymphoid properties.