Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The stimulation of DNA synthesis in lymphocyte populations was previously shown to depend strongly on the intracellular glutathione (GSH) level. Since T cell growth is known to depend on interleukin 2 (IL-2), the experiments in this report were designed to determine whether intracellular GSH depletion may inhibit IL-2 production or the IL-2 dependent DNA synthesis. Our experiments revealed that IL-2 production and DNA synthesis of mitogenically stimulated splenic T cells have indeed different requirements for GSH. The addition of relatively high concentrations of GSH (5 mM) to cultures of concanavalin A (Con A)-stimulated splenic T cells was found to augment strongly the DNA synthesis but inhibited the production of IL-2. Moderate intracellular GSH levels, however, are apparently not inhibitory for IL-2 production, since intracellular GSH depletion by cysteine starvation or by graded concentrations of DL-buthionine sulfoximine (BSO) had virtually no effect on IL-2-specific mRNA expression and the production of T cell growth factor (TCGF). The DNA synthesis activity, in contrast, was strongly suppressed after GSH depletion with either method. As in cultures of splenic T cells, GSH depletion had no substantial effect on the induction of IL-2 mRNA and TCGF production in several mitogenically stimulated T cell clones. Taken together, our experiments suggest that complex immune response may operate best at intermediate GSH levels that are not too high to inhibit IL-2 production but sufficient to support DNA synthesis.
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PMID:Interleukin-2 mRNA expression, lymphokine production and DNA synthesis in glutathione-depleted T cells. 220 8

An H-2-associated immune response gene which maps to the I-A subregion of the H-2 complex governs the ability of H-2 congenic mice to mount an antibody response to five phosphoproteins with molecular weights of 33,000, 29,000, 23,000, 17,000, and 16,000 when inoculated with BW5147, a spontaneous AKR T-cell leukemic cell line. The phosphoproteins are present in all tumor cell lines tested, including those of murine and human origins. The phosphoproteins are associated with the proliferative state of the cell as studied in many systems including growth stimulation of normal lymphoid cells with mitogens, interleukin 2 dependency for growth of a cloned T-cell line, cessation of proliferation by serum starvation of Swiss 3T3 fibroblasts, retention of the proliferative capacity of SV40-transformed 3T3 fibroblasts, and the differentiation and inhibition of proliferation of human promyelocytic leukemic cells. Phosphoproteins with molecular weights of 33,000, 29,000, 23,000, 17,000, and 16,000 are therefore not specific to a particular inducible cellular pathway but are associated with cell proliferation in general.
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PMID:Phosphoproteins recognized by an H-2-linked immune response gene and their association with cell proliferation. 309 5

The question of whether lymphocytes which have once been activated and have completed one or several cell cycle(s) can return to the G0 phase and stay ready for a new activation (G0-G1 transition), rather than simply die, was investigated. To do so interleukin 2 (IL-2) was removed from cultures of continuously proliferating human T lymphocytes and the formation of resting (G0) cells was measured. Kinetic analyses in freshly prepared peripheral blood lymphocytes (PBL) revealed that the onset of detectable RNA synthesis and the appearance of structures binding the anti-Tac antibody occurred simultaneously. This allowed the expansion of the definition of G0 T lymphocytes as cells having a low RNA (and DNA) content, and no Tac antigen. When cultured human T cells proliferating continuously by means of IL-2 were characterized in terms of their distribution in the cell cycle, 7 days after the initial PHA stimulation, it could be demonstrated that very few cells were in the G0 phase, supporting the concept of direct S/G2/M-G1 transition. However, when IL-2 was removed from the cultures, the [3H]thymidine incorporation per 10(4) cells and correspondingly the number of cells in the S/G2/M and G1 phases were reduced drastically and during the following 72-hr period, the number of G0 cells increased markedly. Restimulation of such in vitro formed G0 cells, under conditions permitting observation of their shift from the G0 to G0 phase, demonstrated that most cells could respond normally. Based on these observations, it was concluded that IL-2 not only ensures T-lymphocyte survival and proliferation, but IL-2 starvation induces many continuously proliferating T lymphocytes to stop cycling and to return to the G0 phase of the cell cycle where they remain functional.
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PMID:Lymphokine regulation of human lymphocyte proliferation: formation of resting G0 cells by removal of interleukin 2 in cultures of proliferating T lymphocytes. 661 Apr 79

We have identified the nucleotide sequence of the cDNA encoding the human counterpart of the mouse gene Plk (polo-like kinase). The sequence of the human gene, PLK, predicts a serine/threonine kinase of 603 aa. Expression of PLK mRNA appeared to be strongly correlated with the mitotic activity of cells. Resting peripheral lymphocytes did not express the gene at all. When primary T cells were activated by phytohemagglutinin, a high level of PLK transcripts resulted within 2-3 days. In some cases, addition of interleukin 2 to these cells increased the expression of PLK mRNA further. In contrast, primary cultures of human peripheral macrophages, which were not dividing under the culture conditions applied, showed very little or no PLK mRNA. Stimulation of these cells by bacterial lipopolysaccharide, an inducer of several cytokines in macrophages, totally abrogated the expression of PLK mRNA. In line with a function of PLK mRNA expression in mitotically active cells is our finding that six immortalized cell lines examined expressed the gene. In A-431 epidermoid carcinoma cells this expression was down-regulated by serum starvation and enhanced after serum was added again. Tumors of various origin (lung, colon, stomach, smooth muscle, and esophagus as well as non-Hodgkin lymphomas) expressed high levels of PLK transcripts in about 80% of the samples studied, whereas PLK mRNA was absent in surrounding tissue, except for colon. The only normal tissues where PLK mRNA expression was observed were colon and placenta, both known to be mitotically active. No PLK transcripts were found in normal adult lung, brain, heart, liver, kidney, skeletal muscle, and pancreas. In Northern blot experiments with RNA from lymphocytes which were treated with phytohemagglutinin and cycloheximide, PLK transcripts were not detectable, suggesting that PLK is not an early growth-response gene.
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PMID:Induction and down-regulation of PLK, a human serine/threonine kinase expressed in proliferating cells and tumors. 812 74

Leptin seems to play an important role in the generation and maintenance of immune responses. Leptin is a cytokine similar in structure to interleukin 2, an important T-cell growth factor. Energy balance and supply is increasingly being realised as an important factor in the survival and function of immune cells. Immune responses are intrinsically energy expensive and come at a cost to the responding organism. A fall in leptin concentration, as occurs in starvation, causes impaired cellular immune responses with proinflammatory and Th1 immune responses being particularly affected. Animal models of leptin deficiency show impaired cognate immune responses and are resistant to a variety of autoimmune diseases, mainly those dependent on intact T-cell immunity. The next step is to determine whether modulation of the leptin axis is therapeutically beneficial in a variety of autoimmune or infectious diseases.
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PMID:Role of leptin in immunology. 1240 82

T-cell-mediated immunotherapy is a promising therapeutic option for multiple myeloma (MM). Gamma-delta T cells (gammadelta T cells) recognize phosphoantigens and display strong anti-tumour cytotoxicity. The synthetic agonist Phosphostim (bromohydrin pyrophosphate, BrHPP) has been shown to selectively activate Vgamma9Vdelta2 T cells. This study aimed to evaluate the expansion capacity and anti-myeloma cell cytotoxicity of circulating gammadelta T cells from MM patients at different time points throughout the disease, using Phosphostim and interleukin 2 (IL-2). Circulating gammadelta T cell counts in patients with newly diagnosed MM or in relapse did not differ from those in healthy donors. A 14-d culture of peripheral blood mononuclear cells with Phosphostim and IL-2 triggered a 100-fold expansion of gammadelta T cells in 78% of newly diagnosed patients. Gammadelta T cells harvested at the time of haematopoietic progenitor collection or in relapsing patients expanded less efficiently. Expanded gammadelta T cells killed 13/14 myeloma cell lines as well as primary myeloma cells, but not normal CD34 cells. Their killing efficiency was not affected by 2-d IL-2 starvation. This study demonstrated the ability of Phosphostim and IL-2 to expand gammadelta T cells from MM patients, and the efficient and stable killing of human myeloma cells by gd T cells.
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PMID:In vitro expansion of gamma delta T cells with anti-myeloma cell activity by Phosphostim and IL-2 in patients with multiple myeloma. 1789 96