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Results for “T cell proliferation”

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At least 19 recordsLinked to original sources
PubMed2024

Transient Zn2+ deficiency induces replication stress and compromises daughter cell proliferation.

Cells must replicate their genome quickly and accurately, and they require metabolites and cofactors to do so. Ionic zinc (Zn2+) is an essential micronutrient that is required for hundreds of cellular processes, including DNA synthesis and adequate proliferation. Deficiency in this micronutrient impairs DNA synthesis and inhibits proliferation, but the mechanism is unknown. Using fluorescent reporters to track single cells via long-term live-cell imaging, we find that Zn2+ is required at the G1/S transition and during S phase for timely completion of S phase. A short pulse of Zn2+ deficiency impairs DNA synthesis and increases markers of replication stress. These markers of replication stress are reversed upon resupply of Zn2+. Finally, we find that if Zn2+ is chelated during the mother cell's S phase, daughter cells enter a transient quiescent state, maintained by sustained expression of p21, which disappears upon reentry into the cell cycle. In summary, short pulses of mild Zn2+ deficiency in S phase specifically induce replication stress, which causes downstream proliferation impairments in daughter cells.

Zinc↗
PubMed2023

Transient Zn2+ deficiency induces replication stress and compromises daughter cell proliferation.

Cells must replicate their genome quickly and accurately, and they require metabolites and cofactors to do so. Ionic zinc (Zn2+) is an essential micronutrient that is required for hundreds of cellular processes, including DNA synthesis and adequate proliferation. Deficiency in this micronutrient impairs DNA synthesis and inhibits proliferation, but the mechanism is unknown. Using fluorescent reporters to track single cells via long-term live-cell imaging, we find that Zn2+ is required at the G1/S transition and during S-phase for timely completion of S-phase. A short pulse of Zn2+ deficiency impairs DNA synthesis and increases markers of replication stress. These markers of replication stress are reversed upon resupply of Zn2+. Finally, we find that if Zn2+ is removed during the mother cell's S-phase, daughter cells enter a transient quiescent state, maintained by sustained expression of p21, which disappears upon reentry into the cell cycle. In summary, short pulses of mild Zn2+ deficiency in S-phase specifically induce replication stress, which causes downstream proliferation impairments in daughter cells.

Biological sciences↗
PubMed1979

Cell proliferation and cortical cell production in relation to wool growth.

The relationship of wool growth to cell proliferation in the follicle bulb and to the subsequent migration and growth of the fibre cortical cells was investigated in 10 Peppin Merino sheep. These sheep had been maintained on a low, medium or high level of nutrient intake to ensure a wide range in wool growth. The number and mitotic activity of the germinal cells in the follicle bulb were determined after administration of colchicine. Cortical cell size was measured following isolation of the fibre cells by acid-treatment of wool. The average fibre production of the follicle varied from 4.1 x 10(4) to 13.2 x 10(4) micron3/day in these sheep. There were also substantial differences between sheep in the mitotic activity of the germinal cells in the bulb, the rate of cell proliferation being highly correlated with the average daily fibre production of the follicle (r = + 0.88, n = 10). However, the size of the germinal cell population differed from sheep to sheep and was not closely related to the level of fibre production (r = + 0.48, n = 10). The average turnover time of these cells was inversely related to fibre production and varied from 41.6 to 19.4 h (r = -0.82, n = 10). Multiple regression analysis of the data showed that the average daily fibre production of the follicle was largely determined by the number of germinal cells present in the bulb and their rate of proliferation (R = +0.95, n = 10). Variations in cell turnover time and in cortical cell size were not significant in influencing the rate of fibre production. In these sheep, the average cortical cell varied in size from 658 to 1279 micron 3 and the positive correlation (r = + 0.83, n = 10) found between cell size and fibre production is considered to merely reflect an allometric relationship. The proportion of germinal cells contributing to the fibre cortex was found to be small and variable, ranging from 9.4 to 17.8%. Furthermore, this proportion was not related to the nutritional level of these sheep, and it is thought that the variability in the distribution of cells to the fibre may be attributed to genetic differences between sheep.

Animals↗
PubMed1977

Autoradiographic demonstration of proliferating cells in cerebrospinal fluid.

The proliferative activity of cells, isolated from 82 human CSF specimens, was examined by 3H-thymidine autoradiography. High labelling indices (LI) were found in acute viral meningitis (up to 8 per cent) and radiculitis (up to 6 per cent). CSF cell proliferation was also shown in the subacute stages of viral diseases and in other inflammatory processes (LI ranging from 0.5 per cent to 3 per cent). Most of the cells labelled from these CSF specimens were large lymphocytes, "lymphoid cells" and plasmacytes. Their presence in CSF is presumed to indicate an immune reaction. By the demonstration of a proliferative activity of these cells, aseptic inflammatory processes can be differentiated from "unspecific" pleocytosis. Because of a correlation between the LI of CSF cells and the stages of some inflammations, this method is suggested for an assessment of pregression or remission of chronic processes, e.g. "chronic meningitis" and multiple sclerosis. It can also be used in experimental research: the same type of mononuclear cells was labelled after having been cultured for 23 hours prior to the incubation with 3H-thymidine. Proliferating tumor cells as well as proliferating non-neoplastic mononuclear cells were demonstrated in CSF from various neoplastic diseases. In the clinical diagnosis of these processes, the method is of limited value. It proved very useful, however, for an assessment of the therapeutic effects of intrathecal cytostatic therapy. CSF specimens from non-inflammatory and non-neoplastic diseases regularly contained very few proliferating cells (LI: less than 0.1).

Autoradiography↗
PubMed1979

[Cell proliferation and migration in the roof of the mesencephalon (tectum) in Xenopus laevis tadpoles and adult frogs normally and in brain injury. II. Cell proliferation and differentiation of the tectum in frogs].

The proliferation and directions of cell differentiation in tectum opticum were studied in the young frogs under the conditions of normal development and upon brain trauma by means of 3H-thymidine autoradiography. The same types of cells were shown to be able of proliferation in both the cases: cells of the ventricle zone and glioblasts (gliocytes) in all other tectum layers. A study of directions of the tectum proliferating cells' differentiation in the frogs has shown that the proliferating cells differentiate mainly in the ependyme tanicytes in the ventricle layer 1 and gliocytes in the other tectum layers. The trauma did not change the direction of proliferating cells' differentiation towards the formation of neurons. The complete regeneration is observed in the tectum layer 1 only.

Animals↗
PubMed1978

Polyclonal activation of human B lymphocytes in vitro by pokeweed mitogen: a simple technique for the simultaneous assessment of cell proliferation, generation of plasma cells, plaque-forming cells and immunoglobulin production.

A simple technique has been worked out for the simultaneous assessment of cell proliferation, generation of plasma cells, plaque-forming cells and immunoglobulin production from single cultures of 1 X 10(6) human peripheral blood lymphocytes stimulated with pokeweed mitogen (PWM). Kinetic studies showed that number of cells, thymidine incorporation rate, number of plaque-forming cells against fluorescein-isothiocyanate-haptenated sheep erythrocytes and concentration of IgM and IgG in the supernatant peaked on the average between day 5 and 7 of culture. This technique is particularly suitable for the analysis of hypogammaglobulinaemias in infancy.

Adult↗
PubMed1977

Gastric mucosal cell proliferation and immunoglobulin-containing cells in Ménétriér's Disease.

The amount of immunoglobulin-containing cells in gastric mucosa from 6 patients with Ménétriér's disease was estimated. Furthermore, the rate of gastric epithelial cell proliferation was sutdied in 4 of the patients. Fluorescent antisera specifically reacting with IgA, IgG and IgM were applied, and accordingly the cells were differentiated and quantitated. Other biopsies were labelled in vitro with 3H-thymidine and autoradiographs were prepared. The percentage of DNA-synthesising cells in the progenitor cell region was estimated. The number of IgM-containing cells in the gastric fundic mucosa was markedly increased, while the rate of epithelial cell proliferation was increased in 2 cases and within normal range in the remaining 2 patients.

Adult↗
PubMed1979

Immunoregulation of localized and disseminated murine myeloma: antigen-specific regulation of MOPC-315 stem cell proliferation and secretory cell differentiation.

Tumor development, MOPC-315 stem cells, and M315-secretory cells were quantitated in carrier-primed BALB/c mice that had been challenged subcutaneously or i.v. with mixtures of TNP-carrier and TNP-binding MOPC-315 cells. We observed that tumor incidence, myeloma stem cells, and secretory myeloma cells were: i) suppressed in mice in whom carrier-specific suppressor T cells had previously been induced and ii) initially ehnahced in mice with carrier-specific helper T cells. The early enhancement in mice with carrier-specific helper T cells was followed by progressively declining myeloma stem cell frequencies and regression of established tumors. These studies demonstrate that T cell-derived immunoregulators of host origin can be focused onto localized and disseminated malignant B cells and specifically regulate the expansion and differentiation of the neoplastic clone.

Animals↗
PubMed1979

Lymphocyte subpopulations in man: suppression of PWM-induced B-cell proliferation by infectious mononucleosis T cells.

The in vitro polyclonal pokeweed mitogen (PWM)-induced activation of human B lymphocytes is enhanced by addition of autologous or allogeneic irradiated T cells. This model for B/T-cell cooperation may be used to define and describe the balance between T helper and T suppressor phenomena. The present study investigates the helper and suppressor capacities of mononuclear cells isolated from peripheral blood of infectious mononucleosis patients during the acute disease and the reconvalescence period. During the acute disease we found a functional lack of T helper capacity; furthermore, the T cells were able to suppress the PWM and T-cell-dependent B-cell proliferation of healthy donor cells. The suppression was non-cytotoxic; i.e. not due to destruction of the responder cells. This phenomenon of non-cytotoxic suppression was found for all seven patients studied and disappeared during the reconvalescence period, indicating that the T lymphocytosis seen in infectious mononucleosis includes an expansion of T suppressor cells.

Adolescent↗
PubMed1977

The effects of neuraminidase and galactose oxidase on murine lymphocytes. I. Evidence for the differential delivery of signal(s) leading to cell proliferation and the differentiation of cytotoxic T cells.

The sequential treatment of normal C57BL/6 mouse spleen cell populations with neuraminidase (NA) and galactose oxidase (GO) resulted in cell proliferation, but not in the differentiation of cytotoxic T cells. In contrast, C57BL/6 spleen cells derived from animals primed 5 to 8 months earlier with alloantigen (P815 mastocytoma cells of the DBA/2 strain) both proliferated and demonstrated T cell-mediated cytotoxicity after NAGO stimulation. T cells differentiating into cytotoxic cells after NAGO treatment demonstrated properties similar to alloantigen-specific 'memory' T cells. These were: 1) cytotoxicity developed only from 'primed' cell populations, 2) cytotoxicity developed within 24 hr after NAGO treatment, 3) DNA synthesis was not required for the differentiation of cytotoxic cells during the first 24 hr of culture but both DNA synthesis and cell proliferation were required for the cytotoxicity developing after 24 hr, and 4) all cytotoxicity induced by NAGO showed specificity for the priming alloantigen. It was found, furthermore, that cytotoxicity could be induced at much lower GO concentrations than needed for increased DNA synthesis. We interpret this finding as an indication that NAGO can differentially deliver two 'signals' to T lymphocytes: one leading to cell proliferation, the other causing the differentiation of memory T cells into cytotoxic effectors.

Animals↗
PubMed1979

A simple reliable system for studying antigen-specific murine T cell proliferation.

Antigen-specific T cell proliferation can be readily elicited from the popliteal lymph node cells of mice which have received immunizations of antigen in the hind footpads. The advantages of our system over other published methods are (i) simplicity in method and materials, (ii) much improved reproducibility, (iii) negligible concomitant B cell proliferation, (iv) large degrees of antigen specific proliferation with very low background, and (v) complete dependence of the response on accessory cells or macrophages. These results were brought about by proper immunization procedures for mice and judicious choice of culture conditions. Our data show that the system is very suitable for the study of macrophage-T cell interaction in the induction of T cell proliferation as well as the genetic basis of responsiveness or non-responsiveness to protein and polypeptide antigens.

Animals↗
PubMed1978

Inhibitor of hematopoietic cell proliferation derived from a human leukemic cell line.

A continuously growing human myeloid leukemia cell line (K562) produced a potent high-molecular-weight inhibitor of hematopoietic cell proliferation. It was most active against myeloid stem cells (CFU-C) and proliferating T lymphocytes; it was less active against erythroid precursors (CFU-E) and did not inhibit fibroblasts or established lines of epithelioid cells or B lymphocytes. Inhibition of CFU-C was by direct interaction rather than by modulation of production of colony-stimulating activity and probably occurred at restricted points in the cell cycle. Inhibition could, within limits, be reversed by washing the target cells. Production of inhibitors of hematopoiesis is not a general property of established cell lines, and only two have thus far been identified in screening of 30 such lines.

Bone Marrow Cells↗
PubMed1979

Modulation of cell proliferation and senescence of WI-38 cells by hydrocortisone.

The specific binding of glucocorticoid hormones has been studied in the normal diploid human cell line WI-38. These cells were found to contain high affinity glucocorticoid binding sites whose molecular specificity showed a high correlation to that required for the stimulation of cell growth. When hydrocortisone (HC) was selectively added to or removed from parasynchronously dividing cultures, we observed that HC -enhanced stimulation of cell growth was associated with the hormone's presence in the pre-DNA synthetic period of the cell cycle. Similarly, the specific binding of [3H]dexamethasone in stimulated quiescent cells was found to increase significantly in the pre-DNA synthetic period. The concentration of specific binding sites per cell achieved in stimulated cell cultures was found to decrease with increasing in vitro age. These results suggest that the stimulation of WI-38 cell proliferation by HC involves specific glucocorticoid receptors whose concentration per cell is under cell cycle control. The age-associated decrease in specific glucocorticoid binding sites may explain, in part, our previously observed loss of responsiveness to HC in aging cell cultures.

Cell Cycle↗
PubMed1977

Cell proliferation and histologic classification of bronchogenic carcinoma.

The rate of cell proliferation of 99 bronchogenic carcinomas (94 primary tumors and 5 metastases) was evaluated from the labeling index after in vitro incorporation of [3H]thymidine; the rate was then correlated with the histologic tumor type according to the classification of the World Health Organization (WHO). Cell proliferation was significantly slower in adenocarcinoma (WHO type III) than in squamous cell carcinoma (WHO type I), small cell anaplastic carcinoma (WHO type II), and large cell carcinoma (WHO type IV). Cells proliferated at a significantly higher rate in large cell carcinoma than in the squamous cell type, whereas no significant difference was observed between the other cell types. Dedifferentiated forms of squamous cell carcinomas had a higher rate of cell proliferation than did differentiated forms of the same cell type. Metastases of small cell anaplastic carcinoma did not differ in cell proliferation from primary tumors of the same cell type.

Adenocarcinoma↗
PubMed1977

The influence of adrenoceptor activity on cell proliferation in colonic crypt ipithelium and in colonic adenocarcinomata.

The effects of chemical sympathectomy and of the injection of amines or amine-receptor blocking drugs on cell proliferation in colonic crypts and in dimethylhydrazine-induced colonic carcinomata is examined in rats using a stathmokinetic technique. In animals which had been chemically sympathectomized by injection of 6-hydroxydopamine cell proliferation essentially ceased in the colonic crypts but continued at a normal rate in the tumours. Stimulation of alpha-adrenoceptors by metaraminol, a drug with properties similar to noradrenaline, caused acceleration of cell proliferation in colonic crypts but not in tumours. Conversely, blockade of alpha-adrenoceptors by phentolamine inhibited cell proliferation in crypts but not in tumours. Injection of adrenaline, predominantly a beta-adrenergic agonist, inhibited cell proliferation in the tumours but not in colonic crypts whereas blockade of beta-adrenoceptors by propranolol accelerated cell proliferation in tumours but not in colonic crypts. It is postulated that cell proliferation in the crypts of Lieberkühn in rat colon resembles that in rat jejunum in being controlled by the autonomic nervous system. However, tumour cell proliferation does not appear to be subject to such regulation.

Adenocarcinoma↗
PubMed1979

A study of glial cell proliferation in the molecular layer of the dentate gyrus of the rat following interruption of the ventral hippocampal commissure.

The proliferation of glial cells in the molecular layer of the dentate gyrus in response to lesions of the ventral hippocampal commissure, has been studied autoradiographically following intraventricular injections of 3H-thymidine. Within 24 h of commissurotomy there is an appreciable increase in the number of labeled cells throughout the molecular layer which reaches its peak at approximately 36 h. This generalized glial hyperplasia persists for at least 5--6 weeks and there does not appear to be a secondary re-distribution of the newly-generated glial cells as has been reported after entorhinal lesions (Gall et al., 1979). In semi-thin plastic sections most of the proliferating cells more closely resemble the "medium-shade oligodendrocytes" of Ling et al. (1973) than typical microglia; the reactive astrocytes do not appear to participate in the glial proliferation.

Animals↗