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Biomedical subjects

D G Kilburn

Publications and source records attributed to D G Kilburn.

At least 127 records · Page 7Linked to original sources
PubMed1977

Characterization of suppressor cells in mice bearing syngeneic mastocytoma.

Suppressor cells from syngeneic P815 mastocytoma-bearing DBA/2 mice that inhibit in vitro generation of specific anti-tumor cytotoxicity were characterized. Suppressive activity was almost completely eliminated by treating suppressive spleen cells with anti-theta serum and complement. Treatment with anti-mouse lg serum and complement or with carbonyl iron did not affect their suppressive activity. When suppressive thymocytes from P815 tumor-bearing DBA/2 mice were tested for their capacity to inhibit the generation of cytotoxicity against L1210 cells, a leukemia line in DBa/2 mice, they did not affect the activity, indicating that the supressor cells in the thymocytes of P815 tumor-bearing mice are specific to the tumor. When Ficoll-Hypaque density cell separation was carried out with cytotoxic spleen cells and suppressive spleen cells from 815 tumor-bearing mice, the dense fraction was enriched for kiler cells whereas the suppressive activitty was mainly recovered in the light fraction. Therefore, killer cells and suppressor cells in P815 tumor-bearing mice are thought to be distinct populations.

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PubMed1976

The influence of dissolved oxygen on the mitogen responses of mouse lymphocytes.

Mouse spleen cells incubated at either 30 mm Hg dissolved oxygen partial pressure (pO2) or 160 mm Hg did not differ significantly in their survival or in their proliferative response to the mitogens concanavalin A, phytohemagglutinin or bacterial endotoxin in a subsequent static culture. If the mitogen was added prior to exposing the cells to the controlled dissolved oxygen environment the incorporation of thymidine was always substanstially lower in cells held at 160 mm Hg pO2. This toxic effect of oxygen increased with the time of incubation and was not reversed by the inclusion of 2-mercaptoethanol in the medium. Incubation of cells with mitogen in the absence of oxygen had no deleterious effect on the proliferative response. A comparison of DNA, RNA and protein synthesis in Con A stimulated cells indicated that the predominant effect of oxygen was on DNA synthesis.

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PubMed1976

Synergism between immune complexes and serum from tumor-bearing mice in the suppression of mitogen responses.

Immune complexes either adhering to the cells, or added to cultures, synergized with an inhibitor present in serum to suppress the proliferative response of lymphocytes to specific antigens or to B cell or T cell mitogens. The suppressive effect was dependent on the concentration of both the complex and the serum and was substantially higher when the serum was taken from tumor-bearing, rather than normal mice. Immune complexes alone were not suppressive, but appeared to activate or increase the effectiveness of an inhibitor present in serum. Complexes of syngeneic mouse serum or specifically purified rabbit or sheep antibody, as well as heat aggregated mouse or rabbit Ig, were all effective, whereas heat-aggregated F(ab')2 fragments of rabbit Ig were not, suggesting that any aggregate hearing exposed Fc fragments could mediate synergy. Purified T lymphocytes were equally as sensitive to inhibition as the whole spleen cell population, implying that the suppression acted directly on responding cells rather than via an accessory cell.

Animals↗
PubMed1976

Suppressor cells in the spleens of tumor-bearing mice: enrichment by centrifugation on hypaque-ficoll and characterization of the suppressor population.

Spleen cells from mice bearing methylcholanthrene-induced sarcomas or a mammary adenocarcinoma suppressed the mitogen responses of normal spleen and lymph node cells. Lymph node cells from tumor bearers had no suppressive effects. Centrifugation of spleen cells layered on Hypaque-Ficoll (specific gravity of 1.08) produced a dense fraction which pelleted and a light fraction which was retained at the Hypaque-Ficoll-medium interface. Suppressive activity was not found in either fraction of normal spleen cells. In tumor-bearer spleen cells suppressor activity was greatly enriched in the light fraction. Treatment of the suppressor fraction with anti-theta or anti-Ig serum and complement did not remove suppressor activity. However, the suppressor cells were removed by passage through nylon wool or by carbonyl iron treatment. Also, the population which adhered to plastic Petri dishes contained the suppressor cell activity.

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PubMed1976

Characterization of a T-lymphocyte inhibitor in the serum of tumour-bearing mice.

Sera from mice with large tumours from a variety of tissue types and sources have been shown to contain substances capable of suppressing the proliferative response of normal mouse lymphocytes to concanavalin A (Con A), bacterial endotoxin (LPS) and allogeneic cells. The present paper deals with studies on the nature of these inhibitory materials using mainly a methylcholanthrene-induced rhabdomyosarcoma in DBA/2J mice. It was found that a material responsible for inhibition of the Con A response eluted with immunoglobulins on Sephadex G-150 and eluted with monomeric immunoglobulin on Sephadex G-200. The component of tumour-bearer serum responsible for the suppression of the LPS response of normal lymphocytes eluted from Sephadex G-150 with the alpha and beta globulins and albumin (molecular weight less than 150,000). The immunoglobulin-containing serum fraction from tumour-bearing animals inhibited the mixed lymphocyte response, Con A response, and specific immune response to purified protein derivative (PPD) in allogeneic cell systems. It also inhibited the in vitro primary response of mouse cells to sheep red blood cells, and, to a lesser extent, the response to a T cell-independent antigen (DNP-dextran). The inhibitory activity continued to elute with monomeric IgG on Sephadex G-200 when columns were run in 1640 medium and adjusted to pH 2-5, indicating that an acid dissociable complex was not responsible for inhibitory activity. Inhibitor activity could be removed by absorption on immuno-adsorbents containing goat anti-mouse immuno-globulin, and could be recovered by acid elution from the absorbent. Inhibitor activity was not removed by immunoadsorption on columns prepared with antisera to chicken immunoglobulin.

Adsorption↗
PubMed1976

In vitro induction of cytotoxicity against syngeneic mastocytoma and its suppression by spleen and thymus cells from tumor-bearing mice.

P815 times 2 mastocytoma cells, when injected subcutaneously into syngeneic DBA/2 mice, induced T lymphocytemediated cytotoxicity in the mice. During the course of tumor growth this cytotoxic activity decreased and ultimately the tumor killed the mice. When spleen cells from mice with tumors in the early stages of growth were incubated in vitro with mitomycin C-treated tumor cells, specific cytotoxicity mediated by T lymphocytes was developed. In contrast, spleen cells, taken from mice with tumors at a later stage in their growth, did not develop cytotoxic activity. The unresponsiveness of spleen cells from mice with tumors in the latter stages of growth seemed to be due to the presence of suppressor cells since in vitro development of cytotoxicity by spleen cells from early tumor-bearing mice were inhibited by the addition of spleen cells or thymocytes from mice with progressively growing tumors. Normal spleen cells or thymocytes did not affect the response.

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