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Biomedical subjects

M Feldman

Publications and source records attributed to M Feldman.

At least 487 records · Page 27Linked to original sources

Studies on suppressor T cells in tolerance.

(1) Evidence is provided that tolerance induced in mice to HSA depends on a suppressive mechanism which inhibits the responsiveness of potentially competent cells. (2) the suppression is apparently the function of suppressor T cells which are comparatively radiosensitive and are resistant to cortisone. (3) The cortisone resistant suppressor cells are apparently the progeny of cortisone-sensitive precursors, the differentiation of which into mature suppressors seems to be signalled by antigen. (4) The precursor lymphocytes are comparatively short functioning cells (about 14 days), while the mature suppressor T cells function for at least two months.

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The projection of the lateral geniculate nucleus to area 17 of the rat cerebral cortex. II. Terminations upon neuronal perikarya and dendritic shafts.

The forms of dendrites in layer IV receiving degenerating thalamocortical axon terminals directly on their shafts were examined in serial thin sections. Reconstructions showed these dendrites varied in thickness between 2.5 and 0.5 mum. They had essentially smooth contours and rarely showed evidence of protrusions or spines. They were further characterized by the presence of many synapses along their shafts. Only about one in 12 of these synapses was formed by degenerating thalamocortical axon terminals. These smooth dendrites emerged from neuronal perikarya that also received degenerating axon terminals which formed asymmetric synaptic junctions. Such cell bodies bore both symmetric and asymmetric synaptic junctions, and not all of the latter were caused to degenerated after a thalamic lesion. These postsynaptic neurons appeared to be of two kinds, ones with thin dendrites that often contained closely packed microtubules, and others with thicker dendrites that emerged from the poles of oval perikarya.

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Primary cultures of human spleen macrophages in vitro.

A method for establishing and maintaining primary cultures of human spleen macrophages is described. The cultured cells have been characterized as macrophages by virtue of their adherence, morphology, phagocyte activity, surface Fc receptor, and the production of lysozyme.

Cell Adhesion↗

Specific cytotoxicity in vitro of lymphocytes sensitized in culture against tumor cells.

The production of tumor-specific cell-mediated cytotoxicity following in vitro sensitization of C57BL spleen cells against a syngeneic 3LL Lewis lung carcinoma was studied. Lymphocytes were sensitized on monolayers of the tumor cells for 4-5 days. The cytotoxicity was assayed by measuring the reduction in 3H-leucine and 3H-thymidine incorporation by target cells after interaction with the sensitized lymphocytes. Spleen lymphocytes sensitized on monolayers of 3LL tumor cells caused a high extent of lysis; such cells tested on C57BL or C3H fibroblast targets evoked only a low level of cytotoxicity. C57BL spleen cells sensitized on C57BL fibroblasts caused a low level of cytotoxicity when tested on a 3LL target. Thus cytotoxicity appeared to be tumor specific. The reduced incorporation into protein and DNA of target tumor cells caused by the sensitized lymphocytes was a measure of cell injury, which was more sensitive than direct cell count or uptake of 51CR. Lymphocytes from syngeneic tumor-bearing mice, tested 13-25 days after tumor inoculation, did not manifest in vitro cytotoxicity. On the contrary, such lymphocytes sometimes appeared to have a promoting effect on the tumor cells.

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Suppressor factor secreted by T-lymphocytes from tumor-bearing mice.

Spleen cells from C57BL mice bearing the syngeneic carcinoma 3LL enhanced tumor growth. Tumor growth was also enhanced by a soluble factor found in the media of cultured spleen cells from tumor-bearing animals. This factor suppressed a protective immune response of the host and was found to be a product of T-lymphocytes. Removal of B-lymphocytes and macrophages did not prevent its appearance in the culture media, whereas removal of T-lymphocytes inhibited its appearance. Similar suppressor factors were obtained from C3H mice bearing the 3LL tumor and from mice with other tumors. The suppressing factor produced after the growth of 3LL tumor also enhanced the growth of other tumors. It could act on strains incompatible with the donor of the factor-producing cells. Hence tumor growth was possibly facilitated by soluble products of T-lymphocytes that were found in spleens of tumor-bearing mice and that nonspecifically suppressed immune defense mechanisms.

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An in vitro assay of cell-mediated cytotoxicity. Terminal labeling with 3h-leucine.

A method is described for measuring cell-mediated cytotoxicity, based on the incorporation of labeled leucine into actively synthesized proteins in viable target cells which have survived interaction with effector lymphocytes. The method was studied with in vitro or in vivo sensitized lymphocytes in xenogeneic or allogeneic systems. This method was found to be applicable to quantitative determination of cell-mediated cytotoxicity by in vitro sensitized lymphocytes against a syngeneic tumor.

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Transition from T cell protection to T cell enhancement during tumor growth in an allogeneic host.

The cell-mediated immune response of mice toward a lethal allogeneic tumor was investigated during tumor development. The activity of spleen cells from the tumor-bearing mice was studied by transferring them together with 3LL tumor cells into normal C3H/eb recipient mice. The activity depended upon the time interval between inoculation of the tumor and transfer. Spleen cells taken relatively early, 1 week after tumor inoculation, mediated protection against tumor growth. In contrast, spleen cells taken 4 weeks after tumor inoculation markedly enhanced tumor growth. The tumor-enhancing cells, like the tumor-protecting cells, appeared to be T lymphocytes. The enhancing activity could be transferred by extra cellular medium prepared by incubating the enhancing T cells. Protecting activity could not be transferred by cell-free medium prepared from the protecting T cells. Both activities were found to exist to a relatively slight degree in populations of spleen cells from normal mice. The transition from T cell protection to T cell enhancement might be a determining factor in the outcome of the host-tumor relationship.

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Sensitization of T lymphocytes in vitro by syngeneic macrophages fed with tumor antigens.

We investigated the interaction between T lymphocytes and macrophages in the vitro sensitization of lymphocytes against tumor cells. Spleen cells were sensitized in vitro by syngeneic peritoneal macrophages that had been fed with cell-free antigen preparation of syngeneic tumor cells. The sensitized T lymphocytes acquired specific cytotoxic cells. The sensitized T lymphocytes acquired specific cytotoxic activity in vitro and the capacity to inhingeneic fibroblasts, or the antigen preparation by itself were not able to sensitize the lymphocytes against the tumor.

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Induction of T-cells differentiation in vitro by thymus epithelial cells.

Thymus-reticular epithelial cells (TE-cells) were grown in a cell culture devoid of any lymphocytic elements. These cells were able to induce T-cell differentiation in spleen cells from T-dificient mice as expressed by con-A responsiveness and GvH reactivity. It was also shown that xenogeneic rat TE cells were as effective in the induction of T-cell differentiation in vitro as syngeneic TE cells. This system is therefore ideal for the study of T-cell development.

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Thymus-derived rat lymphocyte receptor for cell surface antigens is a nonserologically defined product of the major histocompatibility gene complex.

Recognition of cell surface antigens by nonsensitized thymus-derived rat lymphocytes is not affected by antisera against immunoglobulin, yet can be effectively blocked by treatment of the lymphocytes with alloantisera raised against lymphoid cells. However, allo antisera induced by nonlymphoid cells do not inhibit recognition. Adsorption of blocking antisera on immunoglobulin-Sepharose columns does not decrease their blocking activity. Absorption of blocking alloantisera with liver and kidney homogenates removes the cytotoxic alloantibodies, yet does not affect the capacity of the antisera to block recognition. Anti-H1-1 alloantisera block antigen recognition only of lymphocytes of strains that share the H1-1 locus. These results suggest that the constant part of the thymus-derived lymphocyte receptor for cell-surface antigens is a product of the rat major histocompatibility locus, which is not identical with the serologically defined antigens.

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