Characterization of 17 human immunodeficiency virus-1 carrier cell lines with T cell, myelomonocyte, or megakaryocyte lineages.

Of 29 hematopoietic cell lines tested for susceptibility to human immunodeficiency virus (HIV)-1HTLV-IIIB infection, all CD4+ cell lines became infected. Continuous culturing of infected cell lines resulted in nine HIV-1 carrier cell lines, including, for the first time, an HIV-1 carrier megakaryoblastic cell line, MEG-01/HIV. The immunophenotypic profiles of a total of 17 HIV-1 carrier cell lines (nine newly and eight previously established cell lines) were compared with their respective parental noninfected cell lines.

Possible new genetic marker for human lymphoid leukemias as detected by ribosomal protein S14 cDNA.

Two polymorphic restriction fragments (bands) were detected in human lymphoid leukemias using restriction enzyme HindIII and a DNA probe coding for the human ribosomal protein S14 gene. Seventy-four leukemia samples of either fresh or cultured cells (54 lymphoid and 20 non-lymphoid) and 28 normal leukocyte samples as controls were examined. Southern blot analysis of their genomic DNA showed that, in addition to seven distinct and invariant bands, two new bands of 3.

Interleukin-2 production by human leukemia cell lines of pre-B cell origin.

Cells of 7 tested human leukemia cell lines of pre-B cell origin (as characterized by immunophenotyping and by the expression of cytoplasmic mu chains, but not by surface immunoglobulins) produced after stimulation with bacterial lipopolysaccharide (LPS) or phorbol myristate acetate (PMA) a lymphokine activity which supported the growth of the interleukin-2 (IL-2)-dependent CTLL-2 cell line. Three pieces of evidence indicate that the secreted lymphokine was functionally and antigenically very similar, if not identical, to human IL-2: (1) The lymphokine supported the growth of murine IL-2-dependent CTLL-2 cells, which did not respond to human lymphokines other than IL-2, but it did not stimulate the growth of murine IL-3-dependent FDC-P2 cells, (2) the biological activity of the lymphokine was inhibited by monoclonal antibody (mAb) anti-human-IL-2, and (3) the proliferation of IL-2-dependent cells in the presence of the active material was completely inhibited by the inclusion of the anti-mouse-IL-2 receptor (IL-2R) mAb. Since leukemia cells of immature B-cell origin also synthesize IL-2R, the human pre-B cell leukemias could represent another type of hematological malignancy where the autocrine processes of IL-2 production and utilization are involved in the expansion of the disease.

Enhancement of interleukin-2 (IL-2) production by 6 different cytokines: heterogeneity among IL-2 producing T cell clones.

The production of interleukin-2 (IL-2) by phytohemagglutinin (PHA)-stimulated human leukemia T cell lines was significantly increased by 6 different cytokines. The most effective cytokines were interleukin-1 alpha (IL-1 alpha) and IL-1 beta; less effective were interferon-alpha (IFN-alpha), tumor necrosis factor-alpha (TNF-alpha), IFN-beta and TNF-beta. The combinations of two cytokines had synergistic or additive effects and increased IL-2 production to a greater extent than either cytokine alone.

A novel cell growth-promoting factor identified in a B cell leukemia cell line, BALL-1.

A novel leukemia cell growth-promoting activity has been identified in the culture supernatant from a human B cell leukemia cell line, BALL-1. The supernatant from unstimulated cultures of the BALL-1 cells significantly promoted the growth of 16 out of 24 leukemia/lymphoma cell lines of different lineages (T, B and non-lymphoid) in a minimal concentration of fetal bovine serum (FBS), and of 5 out of 12 cases of fresh leukemia cells in FBS-free medium. The growth-promoting activity in the BALL-1 supernatant has been further characterized using FPLC chromatography, molecular weight (MW) sieve filtration and dialysis.

Selective enhancement of interleukin 1 beta production in myelomonocytic cell lines by insulin and its related cytokines.

The production of interleukin 1 (IL-1) by lipopolysaccharide (LPS)-stimulated myelomonocytic cell lines ML-1, THP-1 and PL-21 was significantly enhanced by the addition of insulin, insulin-like growth factor (IGF)-I or IGF-II into the cell cultures. The IL-1 activity in the supernatants from cell cultures stimulated with LPS and insulin was completely neutralized by anti-IL-1 beta antibody. Anti-IL-1 alpha antibody had no inhibitory effect.

The immunomodulatory role of IFN-alpha or maltose-stabilized IFN-alpha on T-cell activation.

The effects of human interferon-alpha (IFN-alpha) or maltose-stabilized IFN-alpha (MS-IFN-alpha) on IL-2 production by PHA- or anti-CD3 mAb-stimulated MOLT 16 cells, a human leukemic T cell line, were studied. MS-IFN-alpha is an IFN-alpha-containing powder in which maltose was used as an excipient, and has been shown to have a positive effect on human immunodeficiency virus (HIV)-infected patients. In this study, MS-IFN-alpha powder was dissolved in a culture medium and used for the experiments.

R1-20, a novel monoclonal antibody reacting with a molecule distinct from integrin family, induces homotypic cell aggregation.

R1-20, a novel mAb reacting with a cell surface Ag on normal human lymphocytes and leukemic cell lines, was shown to induce homotypic cell aggregation in leukemic cell lines. This phenomenon was specific to mAb R1-20 because antibodies recognizing CD2, CD7, CD28, and HLA-ABC failed to exhibit homotypic cell aggregation. Induction of aggregation by mAb R1-20 occurred at 37 degrees C, but not at 4 degrees C and required cytoskeletal integrity.

Establishment of leukemia cell lines, BALM-6, BALM-7 and BALM-8 with B-cell characteristics from a patient with acute lymphoblastic leukemia.

Three leukemia cell lines, BALM-6, -7 and -8 were established from the bone marrow of a patient with acute lymphoblastic leukemia. Based on immunophenotypic and the cytogenetic analysis and on the expression of immunoglobulins on both the cell surface and in the cytoplasm, BALM-6, BALM-7 and BALM-8 are clonal leukemic cell populations of B cell origin.

Hodgkin's disease derived cell lines: a review.

A number of so-called "HD cell lines" have been established over the last 10-15 years (Table 1). Or those 15 cell lines we studied, only the cell lines CO, DEV, HD-70, HDLM, KM-H2, L-428, L-540 and SUP-HD1 can be regarded to represent true HD cell lines. According to the immunostaining results and molecular genetic data, these 8 cell lines can be assigned either to the T-cell lineage (CO, HDLM, L-540) or B-cell lineage (DEV, HD-70, KM-H2, SUP-HD1).

Inhibitory versus stimulatory effects of natural human interferon-alpha on proliferation of lymphocyte subpopulations.

Highly purified natural human interferon-alpha (IFN-alpha) inhibited in a dose-dependent manner the proliferation of human peripheral blood lymphocytes (PBL) stimulated with T-cell mitogen concanavalin A (Con A) or with interleukin-2 (IL-2). Contrary to this inhibitory effect, IFN-alpha at the same concentrations significantly increased proliferation of PBL stimulated with B-cell mitogen bacterial lipopolysaccharide (LPS) or with IL-3, and even spontaneous proliferation of PBL was enhanced by IFN-alpha. Proliferation of Con A-stimulated PBL depleted of CD8+ cells was sensitive to the inhibitory action of IFN-alpha, while proliferation of the Con A-stimulated CD4+ cell-depleted PBL was not affected by IFN-alpha.

Effects of tumor necrosis factor alpha, interferon alpha and interferon gamma on non-lymphoid leukemia cell lines: growth inhibition, differentiation induction and drug sensitivity modulation.

The potential role of tumor necrosis factor alpha (TNF alpha), interferon alpha (IFN alpha) and interferon gamma (IFN gamma) in the therapy of non-lymphoid leukemia was studied in ten non-lymphoid leukemia cell lines. All three cytokines tested inhibited the growth of the cell lines. However, a high degree of variability in susceptibility to cytotoxic/cytostatic effect of the cytokines was found among individual cell lines.

Regulation of phospholipase A2 activation and arachidonic acid metabolism in an interleukin-3-dependent macrophage-like cell line.

An interleukin 3 (IL-3)-dependent macrophage-like cell line, 11-1-B3, was newly established from CBA/J mouse bone marrow cell cultures. Assay of eicosanoids in the culture supernatants of the intact and [3H]arachidonic acid (AA)-prelabeled cells showed that, after stimulation with the Ca2+ ionophore A23187, the 11-1-B3 cells synthesized and released relatively large amounts of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) but not LTC4. In addition, 11-1-B3 cells showed Ca(2+)-dependent and alkaline pH-optimal phospholipase A2 (PLA2) activity that preferentially hydrolyzed cleavage of sn-2-arachidonyl- but not sn-2-oleoylphosphatidylcholine.

Bi-phenotypic t(9;22)-positive leukemia cell lines from a patient with acute leukemia: NALM-20, established at the onset; and NALM-21, NALM-22 and NALM-23, established after relapse.

Four leukemia cell lines; NALM-20, established at the onset of leukemia and NALM-21, -22 and -23 established at the relapse of the disease were found to be t(9;22)-positive leukemia lines having the biphenotypic feature of B cell and myeloid cell characteristics. In addition, a polyclonal Epstein-Barr virus-transformed normal B cell line, B250, was established from the peripheral blood at the onset of the disease.

Natural human interferon-alpha augments interleukin-2 production by a direct action on the activated IL-2-producing T cells.

The production of interleukin-2 (IL-2) by Concanavalin A (ConA)-stimulated peripheral blood leukocytes (PBL) from normal human donors was enhanced by natural human interferon-alpha (IFN-alpha). The mechanism of the action of IFN-alpha on IL-2 production was studied further using cloned human leukemic T-cell lines, which produce IL-2 spontaneously and/or after mitogen stimulation. It was found that IFN-alpha alone did not stimulate IL-2 production, but increased it in the activated cells.

Two t(9;22) leukemia cell lines (NALM-24 and NALM-25) with bi-phenotypic characteristics and an EBV-positive B-cell non-leukemia cell line (B262) established from a patient with acute lymphoblastic leukemia.

Based on the immunophenotypic, cytogenetic and genotypic findings, two unique leukemia cell lines, NALM-24 and NALM-25, and an EBV-transformed "normal" B-lymphoblastoid cell line (B262) from a patient with ALL were established and characterized. NALM-24 and NALM-25 are unique in that expression of both show B cell and myeloid cell features with the t(9;22) chromosome in single clonal leukemic cell populations.

Induced natural killer-like cytotoxic function in the TCR delta-1 positive human leukemic T-cell lines.

Four human leukemic T-cell lines with a T-cell receptor (TCR) gamma/delta heterodimer (MOLT-13, MOLT-14, and PEER) or beta/delta-heterodimer (DND-41), as determined by monoclonal antibody (mAb), TCR delta-1, were identified by phenotypic and genotypic analysis. Two similar human leukemic T-cell lines with a TCR alpha/beta heterodimer (CCRF-CEM and MOLT-16) were used in this study. Natural killer (NK)-like activity was investigated in the TCR gamma/delta+ cell lines and TCR alpha/beta+ cell lines induced by exogenous recombinant human IL-2 (rIL-2), or phorbol 12-myristate 13-acetate (PMA).

Esterase Isoenzyme Profiles in Acute and Chronic Leukemias.

Using isoelectric focusing (IEF) a number of carboxylic esterase isoenzymes (EC 3.1.1.

Modulation of methotrexate cytotoxicity with natural interferon upon human leukemia cell line HL-60.

The effect of alpha- and gamma-interferon on methotrexate cytotoxicity against human promyelocytic cell line HL-60 has been evaluated. Synergistic inhibition of proliferation is observed with the combination of methotrexate and gamma-interferon. Enhanced cytotoxic effect of methotrexate with alpha- or gamma-interferon is removed by adding thymidine to the growth medium.

CD28 molecule as a receptor-like function for accessory signals in cell-mediated augmentation of IL-2 production.

IL-2 production by PHA-stimulated MOLT 14 cells (a TcR gamma/delta-bearing human leukemic T cell line) and MOLT 16 cells (a TcR alpha/beta-bearing human leukemic T cell line) was markedly augmented by coculturing with BALL-1 cells ( a human leukemic B cell line), or with recombinant human interleukin-1 alpha (rhIL-1 alpha). We have previously shown that the augmentation of IL-2 production, induced by BALL-1 cells, requires cell to cell contact and is an IL-1-independent pathway. In this report, the expression of the CD28 molecule on MOLT 14 cells and MOLT 16 cells was examined for its role in IL-2 production augmented by BALL-1 cells.

Calcium ionophore but not phorbol ester promotes eicosanoids release by proliferating interleukin-3-dependent bone marrow cells.

Eicosanoid release during multilineage hematopoiesis was assessed using freshly isolated mouse bone marrow cells cultured in the presence of interleukin-3 (IL-3) (10% WEHI-3 culture-conditioned medium). Cells that could release prostaglandin E2 (PGE2) when stimulated with calcium ionophore A23187, but not with phorbol ester (PMA), appeared within 4 days. The cells harvested on day 10 released 42 ng of PGE2/10(6) cells/mL after A23187 stimulation.

[T cell differentiation model based on the expression of T cell receptor chains and genes--study in the human leukemia/lymphoma cell lines].

A total of 33 human leukemia/lymphoma cell lines were classified into 4 groups with respect to the pattern of cell membrane (sm) expression of the CD3 and T cell receptor (TCR) molecules; (i) smCD3+TCR alpha beta (16 cell lines), (ii) smCD3+TCR beta delta (1 cell line), (iii) smCD3+TCR gamma delta (3 cell lines) amd (iv) smCD3-TCR- (13 cell lines), respectively. Using monoclonal antibodies (MoAbs) specific to CD3 (NU-T3), TCR alpha chain (alpha F1), TCR beta chain (beta F1), and TCR gamma chain (C gamma M1), respectively, cytoplasmic (cy) expression of these molecules was determined by immunofluorescence test. Expression of cyCD3 was present in all cell lines regardless of groups.

Establishment and characterization of a clonal human T-cell line, MKB-1 derived from a patient with acute myeloblastic leukemia.

A human T-cell line, designated as MKB-1, was established by cloning procedures in a suspension culture from a peripheral blood of a 17-year-old female patient with acute myeloblastic leukemia. The immunological marker profile of MKB-1 indicated that unlike a myeloid phenotype of the original leukemic cells, the cells were positive for CD3 (both cell surface and cytoplasm), T cell receptor (TcR) alpha/beta heterodimer, CD4, CD5, CD7, CD10, CD57 (Leu7), SN-1 and the cytoplasmic TcR beta chain. These findings indicate the T cell nature of the established cells.

Two pathways for inducing interleukin 2 production in MOLT 16 cells, a human leukemic T-cell line: interleukin 1 pathway and interleukin 1-independent pathway.

Phytohemagglutinin (PHA)-stimulated MOLT 16 cells (a human leukemic T cell line, at a concentration of 2 x 10(6) cells/ml) secreted 6 U/ml of interleukin 2 (IL 2) into the culture supernatant during 24 h culture. When interleukin 1 (IL 1) (5 U/ml) or IL 1-producing cells such as human T cell leukemia virus-1 (HTLV-1)-transformed T cell line, C5/MJ, and myelomonocytic cell line, THP-1-O, were added to the MOLT 16 culture at a concentration of 4 x 10(5) cells/ml, far greater IL 2 production (greater than 65 U/ml) was observed. The activity of soluble IL 1 and membrane-associated IL 1 produced by these accessory (A) cells was completely neutralized by the treatment with anti-human IL 1 antibody.