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Biomedical subjects

G Dennert

Publications and source records attributed to G Dennert.

At least 91 records · Page 5Linked to original sources
PubMed1979

Anti-tumor potential of retinoic acid: stimulation of immune mediated effectors.

Data are presented on the effects of retinoic acid (RA) treatment on the in vivo growth of tumors in two mouse strains. Inhibition of tumor growth as a result of systemic RA injection was observed in three out of seven tumor models. Using adult thymectomized, lethally irradiated and fetal liver (A x TFL) reconstituted mice, we found that inhibition of tumor growth is not due to direct toxic effects of RA but rather appears to be the result of stimulation of thymus-dependent immune-mediated effectors to suppress tumor growth. Results suggest that only strongly immunogenic tumors are sensitive to in vivo retinoid inhibition.

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PubMed1979

Continuously proliferating allospecific T cells. I. Specificity of cooperation with allogeneic B cells in the humoral antibody response to sheep erythrocytes.

Allospecific mouse T cells, positively selected in one-way mixed lymphocyte culture were maintained for 3 yr in tissue culture by sequential restimulation. Such proliferating T cells were tested for their ability to induce a positive allogeneic effect: activating B cells in an in vitro primary humoral response to sheep erythrocytes. It was found that such T lymphocytes could function as helper cells. Helper activity was shown to be specific in that the B cells activated had to share major histocompatibility complex (H-2) antigens with the strain used for selection of the cell line. Intra H-2 mapping showed that antigens coded in the IAk subregion played an important role in the induction of the positive allogeneic effect. Supernatant factors could substitute for the allogeneic T cells in activation of the in vitro humoral response. However, such supernates exhibited no strain specificity. Therefore, the specificity seen in the positive allogeneic effect is presumably a consequence of the alloantigenic recognition receptors intrinsic to the T cells, and not to any biologically restricting properties of the allogeneic effect factor itself.

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PubMed1979

Retinoic acid stimulation of the induction of mouse killer T-cells in allogeneic and syngeneic systems.

The ability of retinoic acid (RA), a potent antitumor agent, to stimulate cell-mediated cytotoxicity (CMC) in mice was investigated. Low doses of RA (5-300 micrograms/mouse/day) administered ip into C57BL/6 mice for 5 days daily or for 1--3 months three times a week before immunization in vivo or in vitro with allogeneic BALB/c S194 myeloma cells led to an enhanced cytotoxic activity of their spleen effector cells. Similarly, in a syngeneic situation injection of RA into C57BL/6 or BALB/c mice before in vitro challenge with EL 4 (C57BL/6) or S194 (BALB/c) tumor cells strongly stimulated CMC. The enhanced cytotoxic activity was effected by thymus-derived lymphocytes (T-cells) and specific for the H-2 histocompatibility antigens in the case of the allogeneic sensitization or specific for tumor antigens in the case of the syngeneic sensitization. Because RA had no effect on the effector step of CMC, RA likely enhanced the induction step of T-CMC. The action of RA was antigen-dependent, and it is therefore a true adjuvant rather than a nonspecific stimulator or polyclonal activator of cytotoxic T-cells.

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PubMed1979

Induction of cell-mediated cytotoxicity by lipoprotein containing histocompatibility antigens.

Lipoprotein was isolated from tumour cells by sonication and ultracentrifugal flotation on KBr gradients. It contained H-2 antigen detectable by antibody binding and induced a primary or secondary cell-mediated cytotoxic response in vitro which was H-2 specific. In a syngeneic model only a secondary cell-mediated response was stimulated and no competitive inhibition of the effector step of cell-mediated lysis could be demonstrated. The implications of these findings are discussed.

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PubMed1978

Effects of retinoic acid on the immune system: stimulation of T killer cell induction.

Retinoic acid (RA), a vitamin A derivative with anti-tumor activity, was assayed for its effects on the immune system in mice. High doses of this compound (1000 microgram/mouse/day) have toxic effects and cause depletion on the peripheral lymphoid organs (spleen, thymus) while leaving the bone marrow cells unaffected. Both the in vivo and in vitro induction of cell-mediated cytotoxicity (CMC) to allogeneic tumor cells is stimulated at least tenfold by low doses (25--300 microgram/mouse/day) of RA while high doses suppress CMC induction. RA is shown to be a specific adjuvant for the induction of cytotoxic thymus-derived lymphocytes (T cells) and not a general T cell mitogen or adjuvant. It does not enhance the proliferative response in the mixed lymphocyte culture nor does it stimulate lymphocyte proliferation in response to the mitogens concanavalin A and phytohemagglutinin. The induction of cooperating T cells and the delayed-type hypersensitivity reaction are also not stimulated by RA. In contrast to the reported stimulatory effects of retinyl palmitate and retinyl acetate, RA does not stimulate the humoral response to erythrocytes. The strong adjuvant effects that RA has on the induction of CMC at low doses may be responsible for its anti-tumor activity.

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PubMed1978

Human lymphoblastoid cell lines as effector cells in mitogen-dependent and antibody-dependent cell-mediated lysis.

Based on reports that both human and murine lymphoblastoid cell lines can effect lysis in antibody-dependent (ADCC) and mitogen-induced (MICC) cell-mediated cytotoxicity, 10 human lymphoblastoid cell lines were investigated for their ability to act as effector cells in these lytic reactions. Four cell lines promoted MICC and ADCC of chicken erythrocytes. MICC was inhibited by subjecting the effector cells to gamma-irradiation, and ADCC was partially inhibited by treating antibody-coated target cells with Protein A from Staphylococcus aureus. The latter finding suggests that antibody plays a role in the cytotoxic reaction. The lytic activity of cultured human lymphoid cells in both MICC and ADCC reactions was, however, quite variable for unknown reasons. Because of this instability human lymphoblastoid cell lines are not a suitable source of effector cells for studying the biological and molecular properties of structures responsible for the lytic reaction.

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PubMed1977

The importance of serologically detectable histocompatibility antigens in the induction and effector step of cell-mediated lysis.

The induction and effector steps of T cell-mediated cytotoxicity (CMC) have been studied using a mouse tumor cell line and its variant, which is deficient in serologically defined (SD) H-2 antigens. In allogeneic mice the SDxcell line induces CMC, while the SD- cell line does not. However, both cell lines can be lysed by xenogeneic rat lymphocytes. Antiserum specific for rat T cells was used to demonstrate that CMC of both targetss is partially due to T cells. In allogeneic or syngeneic mouse systems the SD- cells coupled with the 2,4,6-trinitrophenyl (TNP) residue can neither induce CMC nor serve as targets for CMC, while TNP-coupled SDxcells can serve both as immunogen and as targets. Thus allogeneic or syngeneic mouse T cells do not interact with the TNP group of targets lacking H-2 SD antigens. However, mouse T killer cells sensitized to TNP-coupled cells may lyse TNP-coupled targets carrying different H-2 haplotypes. These experiments show that the induction and effector steps of CMC executed by mouse T cells, using TNP-coupled cells as immunogen or targets, need not necessarily demonstrate restriction with regard to a certain genetically defined H-2 haplotype. The presence of cell surface H-2 SD antigens is however, absolutely necessary for the induction and effector steps of CMC by mouse T cells. Using cold target inhibition assays, it was not possible to demonstrate recognition of the TNP moiety on TNP-coupled SDxcells.

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PubMed1977

Failure of T cells specific for strong histocompatibility antigens to cooperate with B cells for a humoral response.

Thymus-derived lymphocytes (T cells) selected for reactivity to strong histocompatibility antigens over a period of one to twelve months in vitro were tested for their ability to cooperate with bone marrow-derived lymphocytes (B cells) for a humoral response. If cultured with normal syngeneic or allogeneic spleen cells and sheep erythrocytes (SRBC) as immunogen, inhibition of the anti-SRBC response was observed. Similarly, in T cell-free spleen cells the alloreactive T cells did not stimulate a humoral response, indicating that they cannot exert cooperative activity on B cells. Since it was possible that the alloreactive T cells may cooperate with B cells in a humoral response to immunogens carrying histocompatibility antigens, hapten-coupled tumor cells were also used as immunogen. Though it is demonstrated that the alloreactive T cells do recognize the tumor cell immunogen, no stimulation of the B cells for a humoral response against the tumor cell is observed. This result, as well as the finding that the antigenic requirements for T helper cell priming and cell proliferation of the alloreactive T cells are different, suggests that these alloreactive T cells and helper T cells belong to different T cell subsets.

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PubMed1976

Continuously proliferating T killer cells specific for H-2b targets: selection and characterization.

BALB/c (H-2d) thymus-derived lymphocytes sensitized to C57BL/6 (H-2b) alloantigens have been propagated in vitro for over 9 months. These T lymphocytes are specifically cytotoxic to H-2b target cells but are stimulated to proliferate by both H-2b and H-2k spleen cells. This indicates that for these selected cells the antigen requirements for cell proliferation are different from those for cell-mediated cytotoxicity. If not continuously stimulated with allogeneic spleen cells, the cytotoxic cultures fail to divide and rapidly lose their cytotoxic activity. Allogeneic erythrocytes do not stimulate cell proliferation in "quiescent" cell cultures and allogeneic tumor cells do so only in the presence of spleen cells. However, "quiescent" cell cultures display cytotoxicity in the presence of phytohemagglutinin A as do cell cultures which have lost their cytotoxic activity although they proliferate upon allogeneic stimulation. The significance of these findings is discussed.

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PubMed1976

The course of Schistosoma mansoni infection in thymectomized rats.

Inbred rats were thymectomized, irradiated, and reconstituted with T cell-free bone marrow cells. Thymectomized-reconstituted (B rats) and control rats were infected with Schistosoma mansoni cercariae and the number of worms recovered was determined at various times after infection. The extent of immunosuppression was assessed by two criteria: 1) response to an injection of sheep erythrocytes (plaque assay, hemagglutination, hemolysis); 2) response to schistosome antigens (passive hemagglutination). Humoral responses to worm antigens were completely suppressed in almost all instances and anti-sheep erythrocyte responses showed a more variable but always very definite depression in B rats. The number of worms in B rats was about 4 times higher than in control animals at 5 weeks and about 3 times higher at 6 weeks. In a different experiment, rats were perfused at 4, 6, and 9 weeks after infection and the number of worms was found to be consistently higher in B rats, by a factor of about 2 at 4 weeks to a factor of about 4 or 6 at subsequent times. Although B rats had more worms than controls even at 9 weeks, a slow drop in their worm burden was noticeable with time in both experiments. Moreover, the size of worms in B rats was smaller than in controls and even 9-week-old worms failed to develop to normal size and appearance and could not be shown to produce fertile eggs. These experiments show a definite involvement of the immune system in the "self-cure" phenomenon, but may at the same time suggest that other non-immune mechanisms are involved in determining the pattern of S. mansoni infection in the rat.

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