concanavalin-a and Lymphoma--T-Cell

Aqueous extracts of the leaves of Larrea divaricata Cav. exert antimitogenic effects on tumor cells (BW 5147 murine immature T-lymphoma) and normal, stimulated lymphocytes. The effective concentration was four times smaller in the case of tumor cells than in the case of normal, stimulated lymphocytes. Inhibitor studies of arachidonate pathway suggest that the proliferative effect of the extract is due to the activation of lipoxygenase metabolism, while the inhibitory action could be a direct effect.

Topics: Animals; Antineoplastic Agents; Arachidonic Acid; Cell Division; Concanavalin A; Cyclooxygenase Inhibitors; Dithizone; Lipoxygenase Inhibitors; Lymphocytes; Lymphoma, T-Cell; Masoprocol; Mice; Plant Extracts; Plant Leaves; Plant Lectins; Tumor Cells, Cultured

The present investigation was carried out to study the effect of tumor growth on the spleen of an aged host. Dalton's lymphoma (DL), a spontaneous T cell lymphoma, was grown in mice of different age groups classified as young, adult or old on the basis of their reproductive status. Splenocytes obtained from normal and tumor-bearing young, adult and old mice were checked for an in vitro blastogenic response to concanavalin A (Con A), colony-forming ability and apoptosis. There was an enhanced apoptosis of splenocytes and a concomitant inhibition of splenocyte blastogenesis and their responsiveness to the mitogenic stimulus of Con A in aged mice. The counts of granulocyte macrophage- and macrophage-colony forming units were significantly enhanced in the spleen of tumor-bearing adult mice. It is proposed that the DL-growth-dependent increase in the size of the spleen in adult mice is due to an increased blastogenesis of splenocytes, which, however, may not be applicable in the case of old tumor-bearing mice. The role of splenic macrophages in the regulation of the functions of the spleen by macrophage-derived NO is shown.

Topics: Aging; Animals; Apoptosis; Cell Survival; Colony-Forming Units Assay; Concanavalin A; Female; In Vitro Techniques; Lymphocyte Activation; Lymphoma, T-Cell; Macrophages; Male; Mice; Mice, Inbred BALB C; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Spleen

Stimuli that are mitogenic for mature T-cells induce cell cycle arrest in some T-cell tumors and T-cell hybridomas. The molecular mechanism of this growth inhibition is poorly understood. In this report, we show that in EL4, a murine T-lymphoma cell line, stimulation with concanavalin A or treatment with phorbol 13-myristate 12-acetate (PMA) inhibit growth, due to cell cycle arrest at both the G1 and the G2/M phases. The block at the G1 phase is accompanied by the appearance of a hypophosphorylated form of the retinoblastoma protein (pRb), due to the inhibition of G1 cyclin-Cdk complexes. However, the molecular mechanisms leading to this G1 cell cycle arrest differ between concanavalin A and PMA: concanavalin A inhibits both cyclin E-Cdk2 and cyclin D-Cdk4 complexes, while PMA inhibits only cyclin E-Cdk2. We demonstrate that concanavalin A inhibits cyclin D-Cdk4 activity by decreasing the amount of cyclin D. The inhibition of cyclin E-Cdk2 by both concanavalin A and PMA is due to increased binding of the Cdk inhibitor p21 to this complex. However, while stimulation of the cells with concanavalin A did not result in an evident increase of the total level of p21, treatment of the cells with PMA increased p21 levels significantly. Our results indicate, furthermore, that the G2/M block results from the inhibition of cyclin A- and cyclin B1-associated kinase activities. As for cyclin E-Cdk2, the inhibition of the cyclin A-Cdk2 complex is due to increased binding of the p21 inhibitor.

Topics: Animals; Concanavalin A; Cyclin-Dependent Kinases; G1 Phase; G2 Phase; Humans; Lymphoma, T-Cell; Mice; Mitosis; Okadaic Acid; Phorbol Esters; Phosphorylation; Tetradecanoylphorbol Acetate; Tumor Cells, Cultured

The clonal expansion of antigen-stimulated T-lymphocytes during an immune response is mediated by several lymphokines. Strong evidence now exists that the neuroendocrine hormone PRL is necessary, but not sufficient, for T-cell proliferation. Little is known, however, of the signal transduction mechanisms of the PRL receptor (PRLR) within T-cells. We demonstrate here that PRL stimulation of the T-cell line Nb2 induced the concentration- and time-dependent activation of the protein tyrosine kinase p59fyn, but not of four other src family protein tyrosine kinases. Activation of fyn was also observed in Concanavalin-A-primed peripheral blood lymphocytes stimulated with PRL and in Nb2 cells incubated with anti-PRLR antibodies. The activation of fyn by PRL stimulation correlated with Nb2 cell proliferation. Immunoblot analysis of anti-fyn and anti-PRLR immune complexes revealed an association between each PRLR isoform and p59fyn. These studies demonstrate for the first time an association between the PRLR and a src family protein tyrosine kinase affiliated with signal transduction.

Topics: Animals; Antibodies, Monoclonal; Cell Division; Cell Line; Concanavalin A; Dose-Response Relationship, Drug; Enzyme Activation; Immunoblotting; Isoenzymes; Lymphocytes; Lymphoma, T-Cell; Phosphorylation; Precipitin Tests; Prolactin; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-fyn; Rats; Receptors, Prolactin; Signal Transduction; T-Lymphocytes; Time Factors; Tumor Cells, Cultured

The Tpl-2 locus, cloned by provirus tagging from one of three sublines of the Moloney leukemia virus-induced rat thymoma 2769, defines a gene encoding a protein kinase associated with progression in 22.5% of the tumors. Tpl-2 is expressed primarily in spleen, thymus, liver, and lung. Provirus integration occurs in the last intron of the gene, leading to the expression of a truncated mRNA that terminates in the proviral long terminal repeat and encodes a protein with an altered C-terminal domain. Strong evidence that this genetic change confers growth advantage to affected cell clones was provided by the finding that, during cultivation of all three sublines derived from tumor 2769, cells were selected that harbored independent provirus insertions in the Tpl-2 locus. Exposure of normal rat spleen cells to Con A induces the expression of enhanced levels of Tpl-2 within the first 60 min from the time of exposure suggesting that, in normal splenocytes, Tpl-2 may be involved in the transition from a quiescent to the G1 phase of the cell cycle.

Topics: Amino Acid Sequence; Animals; Base Sequence; Blotting, Northern; Blotting, Southern; Cells, Cultured; Concanavalin A; DNA Probes; DNA, Neoplasm; Liver; Lung; Lymphocyte Activation; Lymphoma, T-Cell; MAP Kinase Kinase Kinases; Molecular Sequence Data; Moloney murine leukemia virus; Oligodeoxyribonucleotides; Poly A; Polymerase Chain Reaction; Protein Kinases; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Rats; Rats, Inbred F344; Restriction Mapping; RNA; RNA, Messenger; Spleen; T-Lymphocytes; Tumor Cells, Cultured

Interferon regulatory factor-1 (IRF-1) gene expression is rapidly upregulated in the prolactin (PRL)-activated Nb2 rat T lymphoma cell line. To further elucidate its role as a T cell activation molecule, IRF-1 gene expression in response to various T cell stimuli was examined. In Nb2 T cells, PRL induced two peaks of IRF-1 gene expression: a rapid, transient peak at 1 h and a sustained peak at 12 h. PRL subsequently induced interferon-gamma (IFN-gamma) gene expression at 3-6 h. However, the early induction of IRF-1 and IFN-gamma does not appear to be interdependent. Interleukin-2 (IL-2) also induced IRF-1 gene expression in Nb2 T cells but only one broad peak at 10 h was observed. In primary mouse splenocytes, concanavalin A induced rapid and transient expression of the IRF-1 gene; maximal expression occurred by 6 h, and then returned to basal levels by 12-15 h. These results provide additional evidence for the importance of IRF-1 in T cell activation.

Topics: Animals; Cells, Cultured; Concanavalin A; DNA-Binding Proteins; Gene Expression Regulation, Neoplastic; Interferon Regulatory Factor-1; Interleukin-2; Lymphoma, T-Cell; Mice; Mice, Inbred BALB C; Neoplastic Stem Cells; Phosphoproteins; Prolactin; Rats; Receptors, Cell Surface; Recombinant Proteins; RNA, Messenger; Signal Transduction; Stimulation, Chemical; T-Lymphocytes; Tumor Cells, Cultured

It has been demonstrated that the single autosomal recessive lpr and gld genes are responsible for the accumulation of unusual T-cell subsets. Although these subsets have been assigned to the T-cell lineage, they share certain antigenic cell surface markers with mature B lymphocytes. Consequently the maturational pathway(s) of these cells has been difficult to fit in the currently accepted models of T-cell differentiation. Previous work has determined that the YE1/19.1 monoclonal antibody (mAb), developed against the EL4 tumour line, reacts with the accumulating T cells in lpr-expressing mice. In this study we report that YE1/19.1 could also be used as a marker for the accumulating T cells in gld-expressing mice and that the hyporesponsiveness seen in gld mice correlated with these accumulating cells. We then demonstrated that the YE1/19.1 antibody also reacts with a subpopulation of neonatal thymocytes as well as a mitogen non-responsive subpopulation of 'double negative' T cells from the spleens and thymuses of non-autoimmune mice. Our findings indicate that the YE1/19.1 mAb will be a useful probe for helping in the eludication of the intra-thymic maturational pathways of T lymphocytes.

Topics: Animals; Antigens, Neoplasm; Autoimmune Diseases; Cell Division; Concanavalin A; Epitopes; Immune Tolerance; Lymphatic Diseases; Lymphoma, T-Cell; Mice; Mice, Inbred C57BL; T-Lymphocyte Subsets; T-Lymphocytes

The effect of human colostrum on T cell immune function was investigated. Colostrum inhibited the proliferation of human T cells activated by allogeneic, concanavalin A (Con A) or phytohaemagglutinin (PHA) stimulation. Colostrum also inhibited the production of IL-2 by Con A-activated human peripheral blood T cells and by Con A-activated Jurkat cells, a human T lymphoma line. Similarly, human colostrum inhibited the production of IL-2 by EL4 cells, a murine thymoma line, when stimulated with phorbol myristate acetate. The inhibitory activity was not cytotoxic and could not be neutralized by antibody to transforming human growth factor beta.

Topics: Cell Survival; Colostrum; Concanavalin A; Dose-Response Relationship, Drug; Humans; Interleukin-2; Lectins; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Lymphoma, T-Cell; Phytohemagglutinins; T-Lymphocytes; Tetradecanoylphorbol Acetate; Thymoma; Thymus Neoplasms; Transforming Growth Factor beta

The effect of TBG on the functional activity of different cell lines, spontaneous and Con A induced proliferation of PBL was studied. If concentration of TBG is higher than 50 mu kg/ml it suppresses the proliferation in many used cell lines, except choriocarcinoma and cancer of uterus. The reliable increasing of spontaneous proliferation of PBL, Jurkat and K-562 cells may be observed if concentration is more lower (0.5-15 mu kg/ml). However proliferation of other cell lines corresponds to control level, and Con A induced proliferation of PBL is inhibited. The effect was more marked at 48, as compared to 24 hours of cell incubation with TBG.

Topics: Biomarkers, Tumor; Cell Division; Cell Line; Choriocarcinoma; Concanavalin A; Female; HeLa Cells; Humans; Leukemia, Erythroblastic, Acute; Leukemia, Myeloid; Leukemia, T-Cell; Lymphocytes; Lymphoma, B-Cell; Lymphoma, T-Cell; Pregnancy-Specific beta 1-Glycoproteins; Tumor Cells, Cultured; Uterine Neoplasms