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D Naor

Publications and source records attributed to D Naor.

At least 73 records · Page 4Linked to original sources
PubMed1982

Delayed-type hypersensitivity induced in immunodeficient mice with syngeneic modified self antigens: a suggestive model of autoimmune response.

Previous studies suggested that trinitrophenyl (TNP)-modified syngeneic red cells induced humoral autoimmune response in mice with defective T cell function but not in normal mice. The ability of modified self antigen to induce autoimmune response in immunodeficient mice was further explored using the delayed-type hypersensitivity (DTH) as an assay system. Mice were immunized with syngeneic TNP-modified spleen cells (TNP-SC) and challenged by syngeneic nonmodified concanavalin A (Con A) or lipopolysaccharide (LPS)-stimulated spleen cells injected into their footpads. The DTH response was assessed 24, 48 and 72 h later by measuring the footpad swelling and was transferred to naive recipients with enriched T cells from TNP-SC-immunized irradiated A mice but not with serum or non-T cells. Adult thymectomized, X-irradiated (250 rds) and cyclophosphamide-treated mice injected with syngeneic TNP-SC generated a DTH response when subsequently challenged with syngeneic lymphoblasts (induced with Con A or LPS) but not when challenged with allogeneic blast cells. In contrast, normal mice treated in a similar manner exhibited a much less significant DTH response. SC incubated 1 to 3 h with Con A failed to elicit the DTH response of immunodeficient mice previously injected with TNP-SC. Both lymphoblasts that were induced in vitro with Con A diluted in fetal calf serum or in normal mouse serum-containing media, and lymphoblasts that were induced in vivo by interleukin 2 elicited DTH responses in X-irradiated, TNP-SC immunized mice. The syngeneic DTH response of the immunodeficient mice injected with TNP-SC was abrogated when they were simultaneously transplanted with syngeneic SC or nylon wool-passed syngeneic SC. If the transplanted splenocytes had been treated with anti-Thy-1 antiserum and complement they failed to abrogate the syngeneic-DTH response of the above mentioned mice. This result suggests that suppressor cells are programmed to control the autoimmune response induced with modified self antigens.

Animals↗
PubMed1982

Immunogenicity of subcellular fractions and molecular species of MuLV-induced tumors. III. Stimulation of syngeneic antitumor responses by subcellular fractions and molecular species of Moloney virus-induced tumors in CBA and A mice.

YBA, a Moloney virus-induced leukemia in CBA mice, and a relatively weak immunogenic tumor, was screened for the presence of immunogenic antigens. The tumor was subjected to homogenization and subcellular fractionation on sucrose gradients; the immunogenic subcellular fractions underwent further separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The immunogenicity of the subcellular fractions and the SDS-PAGE-isolated molecular species were tested by (their) subcutaneous injection into syngeneic mice and examination of their splenocytes examined against tumor cell and normal cell targets by the chromium release cell-mediated lympholysis assay. Tumor cell homogenates were also separated by SDS-PAGE and tested for immunogenicity without prior fractionation. Splenocytes from mice that had received injections of certain SDS-PAGE-isolated epitopes derived from YBA tumor homogenate or its light and heavy subcellular fractions generated effective cytotoxic responses against YBA target cells after 6 days in vitro cultivation. In contrast, intact YBA tumor cells or non-separated tumor homogenates failed to induce an efficient cytotoxic response. The effector cells induced with the immunogenic SDS-PAGE-isolated epitopes of YBA tumor were specific, since they cytolysed the homologous target cells more efficiently than unrelated target cells or syngeneic normal cells. The activity of these effector cells was affected by varying the effector: target ratio. Augmentation of the cytotoxic responses was obtained when the splenocytes of mice immunized with SDS-PAGE-isolated epitopes of YBA tumor were restimulated in vitro, with the homologous neoplastic cells. Immunogenic SDS-PAGE epitopes were isolated from YAC tumor also (YAC is a Moloney-induced tumor of A mice). The effector cells induced with these separated epitopes were characterized as thymus-derived cells and not as natural killer cells. The results suggest that (1) the molecular repertoire of YBA and YBA tumors contain immunogens that can induce a specific antitumor cell-mediated response; (2) the isolated molecular species injected are more efficient immunogens than the entire, unseparated homogenate sample or a dose of 10(8) intact inactivated tumor cells; and (3) the gel matrix may be responsible for the enhanced cell-mediated response induced against the weakly immunogenic tumor.

Animals↗
PubMed1982

Induction of antitumor reactive cells or suppressor cells by different molecular species isolated from the same nonimmunogenic tumor.

The inability of spontaneous and some laboratory-induced tumors to stimulate the immune system has continuously raised the question of the validity of using immunological maneuvers in order to control tumor growth. In this project we suggest that a tumor which is nonimmunogenic still has an immunogenic potential that can be revealed and used in order to stimulate antitumor immunity and consequently tumor destruction. YAC, a Moloney-virus-induced tumor of A mice, failed to stimulate immunological responses. This tumor homogenate was exposed to nonreduced sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). At the end of the electrophoresis, the gels were sliced and injected in sequential order into various groups of A mice. It was found that some of the gel slices (usually with M.W. of 100 K or less) induced cytotoxic responses, whereas other gel slices (usually with M.W. of about 150 K) induced suppressor cells. Similarly, certain gel slices induced cells that inhibited the in vivo tumor growth, whereas others enhanced the in vivo tumor growth. These last two types of cells did not present the same cellular population that mediated the cellular cytotoxicity or the suppressive effects respectively. It was concluded that poorly immunogenic tumor cells do possess immunogenic potential that can be revealed after dissociation between the immunogenic and suppressogenic entities.

Animals↗
PubMed1982

Control of autoimmune responses induced with modified self antigens.

Our previous studies suggested the TNP-modified syngeneic red blood cells induced a humoral autoimmune response in mice with a defective T cell function but not in normal mice. This report describes the continuation of these studies in which we elucidated the auto-delayed-type hypersensitivity response of mice with a defective T cell function. The mice were immunized with syngeneic TNP-modified spleen cells and challenged 14 d later by injecting syngeneic nonmodified con A-stimulated spleen cells into the footpad. The DTH response was assessed 24 hr later. Adult thymectomized, x-irradiated (250 rad), and Cy-treated mice injected with syngeneic TNP-Sc generated a DTH response when subsequently challenged with syngeneic blast cells but not when challenged with allogeneic blast cells. In contrast, normal mice treated in a similar manner did not exhibit a significant DTH response. The auto-DTH response of x-irradiated mice injected with TNP-Sc was abrogated when they were simultaneously transplanted with syngeneic spleen cells or nylon wool-passed syngeneic spleen cells. If the transplanted splenocytes had been treated with anti-Thy 1 serum and complement, they failed to abrogate the auto-DTH response of the above-mentioned mice. These results suggest that suppressor cells are programmed to control the autoimmune response induced with modified self antigens.

Aging↗
PubMed1981

Immune response to weakly immunogenic virally induced tumors. IX. Mice injected with the in vitro variant of YAC tumor (YAC-1) resist lethal doses of the tumorigenic YAC cells.

The ability of the in vitro propagated syngeneic tumor YAC-1 and the allogeneic tumor RBL5 to stimulate cytotoxic cells in A mice, was in correlation with the ability of these tumors to impose in vivo resistance to the viable YAC cells. Similarly, the ability of allogeneic YAC-1 tumor and syngeneic RBL5 tumor to stimulate cytotoxic cells in C57BL/6 mice was in correlation with the ability of these tumors to impose in vivo resistance to the viable RBL5 cells. In contrast, the original in vivo carried YAC tumor cells that induce the appearance of suppressor cells, as measured by in vitro assay, stimulated the in vivo enhancement of tumor growth in A mice. Adult thymectomy delayed the death of A mice injected with viable YAC cells, suggesting that at least some of the cells participating in the tumor enhancement are thymus derived cells.

Animals↗
PubMed1980

Immune responses to weakly immunogenic murine-leukemia-virus-induced tumors. VII. Kinetic studies on various parameters of effects induced with suppressor cells.

YAC, a Moloney-virus-induced tumor of A mice, caused an inhibition of specific immunologic responses in A and C57BL/6 mice, which was mediated by suppressor cells. In contrast, YAC-1, the in vitro-carried tumor derived from cultivated YAC cells, stimulated the appearance of antitumor reactive cells in A mice. Splenocytes from YAC-1-injected mice generated anti-YAC cytotoxic cells after six days of culture. The suppressor cells from YAC-injected mice efficiently inhibited the cytotoxic responses of the cultivated reactive cells (YAC-1-primed cells) when added at the start of the culture, but not when added at later times. Suppressor cells appeared in A mice three days after injecion of YAC cells and persisted in the animals for at least 50 days. YAC-1-primed cells, derived from A mice 1, 3, 9 and 20 days after injection of YAC-1 cells, were sensitive to the suppressor cells.

Animals↗
PubMed1980

Immune responses to weakly immunogenic murine-leukemia-virus-induced tumors. VIII. Characterization of suppressor cells.

YAC is a Moloney-virus-induced tumor of A mice. YAC-injected A and C57BL/6 mice generated suppressor cells. The suppressive function of the cells was tested by determining the ability of splenocytes from YAC-injected mice to inhibit the in vitro cytotoxic responses of primed splenocytes. It was found that suppressor cells passed through a nylon-wool column did not adhere to the plastic surface and resisted treatment with rabbit antimouse brain serum and guinea-pig complement. Therefore, the suppressor cells were defined operationally as "null" complement. Therefore, the suppressor cells did not demonstrate high efficiency; a relatively high concentration of suppressor cells was required to achieve an effective inhibiting action. These findings are discussed in terms of the heterogeneity of suppressor cells.

Animals↗
PubMed1980

Studies on the immune response to fixed antigens. IV. Recall of immunologic memory with fixed antigens.

The chemically modified antigens, trinitrophenylated sheep red blood cells (SRBC) and glutaraldehyde-SRBC, elicited specific secondary responses in mice but were unable to induce primary responses. They also induced specific immunologic memory. The secondary immune response was directed to the specific determinants of SRBC but not to new antigenic determinants created by the chemical modification process. The interpretation of these findings is discussed in relationship to the ability of fixed antigens to be processed by macrophages.

Animals↗
PubMed1979

Immune responses to weakly immunogenic virally induced tumors. III. Genetically unrestricted cytolysis of allogeneic tumor target cells.

Splenocytes from A mice injected with YAC-1 or RBL5 could generate, after in vitro culture with or without stimulation, a genetically nonrestricted cytotoxic response against the allogenic tumor RBL5. YAC-1 tumor is an in vitro carried tumor induced in A mice (H-2a) by Moloney virus. RBL5 tumor is a Rauscher virus-induced tumor of C57BL/6 mice (H-2b). These tumors cross-react serologically. The effector cells that were generated after the in vitro cultivation recognized tumor-associated antigens on the target cells. H-2 alloantigens were not recognized by the effector cells. The effector cells that killed RBL5 tumor in a genetically nonrestricted manner were identified as T cells. The in vivo carried tumor YAC, in contrast to the in vitro carried tumor YAC-1, could not induce anti-RBL5 reactive cells in A mice. Instead, YAC tumor induced suppressor cells in A mice, which could abrogate the anti-RBL5 cytotoxic response of RBL5-primed splenocytes, but not that of YAC-1 primed splenocytes.

Animals↗