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Biomedical subjects

D W Talmage

Publications and source records attributed to D W Talmage.

At least 19 recordsLinked to original sources

Enhancement of the primary cytotoxic response to membrane by a lymphokine costimulator.

The primary and secondary cytotoxic T cell responses of C57Bl/6 (H-2b) mouse spleen cells to P-815 membrane fragments (H-2d) were examined. The primary response required the addition of a supernatant from mitogen-stimulated spleen cells, or costimulator, to the culture medium. Costimulator had little effect on the secondary response unless the spleen cells were first passed through a nylon wool column. Our data suggested that secondary cultures produced their own costimulator and that adherent cells were required for its production. The possibility that adherent cells are needed to activate helper cells is discussed.

Animals

Immunosuppression by a mouse tumor resembles antigenic competition.

The intraperitoneal injection of gamma-radiated, UV-radiated, or unradiated P-815 tumor cells into syngeneic or allogeneic mice suppressed the immune response to a subsequent intraperitoneal injection of sheep erythrocytes in a manner similar to the suppression caused by the injection of manner similar to the suppression caused by the injection of horse erythrocytes and termed antigenic competition. In both cases, the greatest suppression occurred when the sheep erythrocytes were injected at the same site (intraperitoneal) as the tumor or antigen several days after the tumor or antigen and in a dose of 10(8) erythrocytes or less.

Animals

The effects of different conditions of organ culture on the survival of the mouse pancreas.

The effects of different conditions of organ culture on the viability of murine pancreatic tissues and, particularly, of pancreatic islets, was assessed by morphologic and histochemical analyses. High oxygen tension (1300 mm Hg), found previously to allow successful allogeneic thyroid transplantation, was toxic to pancreatic tissue. Low temperature (22 degrees C) was associated with better islet preservation than high temperature (37 degrees C). Hydrocortisone did not reduce the survival of pancreatic islets and did appear to preserve the acinar components. Fetal and neonatal pancreas responded similarly to the various organ culture conditions. These results have potential importance in guiding future transplantation experiments.

Animals

Effect of oxygen pressure during culture on survival of mouse thyroid allografts.

A marked increase in the percentage of mouse thyroids that retained function 20 days after transplantation across a major histocompatibility barrier and the percentage that lacked generalized infiltration was observed when the grafts received hyperbaric oxygen during a 4-day culture period. Perfusion of the donor animal before thyroidotomy and the addition of fetal calf serum to the culture medium did not have a significant effect on graft survival, but the percentage of grafts lacking generalized infiltration was slightly increased by the addition of hydrocortisone to the culture medium.

Animals

Immunological induction of T lymphocytes: role of antigen and the lymphocyte costimulator.

In vitro T cell activation requires both antigen presentation and a second stimulus provided by the lymphocyte costimulator. Neither alone is sufficient to induce specific T cell activation. The S+ phenotype of stimulating cells is dependent on the metabolic activity of these cells. This finding is consistent with the notion that production and/or release of the costimulator is a function of metabolically active cells. The costimulator acts at an early stage of the interaction between lymphocyte and antigen, and the costimulator, or a separate maintenance factor, is required throughout the culture period for the expression of full cytotoxic activity. The lymphocyte costimulator is not strain specific but is phylogenetically specific. The activation of cytotoxic T cells by S+ cells is also phylogenetically specific, and this specificity of cellular activation can be accounted for by the species specificity of the lymphocyte costimulator.

Animals

Suppression of in vitro cytotoxic response by macrophages due to induced arginase.

Arginine was found to be completely depleted from cell-free supernates of mixed leukocyte cultures suppressed by the addition of excess macrophages. Partial reversal of macrophage-mediated suppression was accomplished by daily addition of a cocktail containing arginine and nonamino acid nutrients. Complete reversal of the suppression was accomplished by the addition of arginine and glucose to the medium and the nonadherent cells after their separation from the adherent macrophages. A marked increase in the enzyme arginase was found in macrophages that had been cultured 24 h in vitro in Eagle's minimum essential medium plus 10% fetal calf serum, in peritoneal cells activated by prior injection of thioglycollate, and in one spleen activated by a graft vs. host reaction.

Animals

Activation of cytotoxic T cells by nonstimulating tumor cells and spleen cell factor(s).

The ability of three cultured mouse tumor lines to stimulate a cytotoxic response in 5-day cultures of allogeneic lymph node cells was studied with a 51Cr release assay. Two lines of mesenchymal origin, P815 and EL-4, were found to be highly stimulatory, whereas the third cell line, CaD2, a mammary gland epithelial tumor, did not stimulate over a wide range of cell concentration. CaD2 cells were shown to contain major antigens similar to those of P815 cells by the specific lysis of both cells by lymphocytes activated to H-2d-bearing peritoneal cells.UV-irradiated P815-cells, like gamma-irradiated CaD2 cells, did not stimulate a cytotoxic response, but both cell lines were found to stimulate a full and specific response to allogeneic lymph node cells if these mixed cultures were supplemented with a supernatant harvested from concanavalin A-stimulated spleen cells.

Animals

The requirement of viable thymocytes for species-specific attachment to and release from macrophages.

The role of the thymocyte in its species-specific binding to macrophages has been explored. Although formalin treatment of macrophages resulted in loss of binding to thymocytes, formalin treatment of thymocytes did not have this effect. However, two differences between living and formalin-treated thymocytes were noted. Formalin-treated thymocytes bound to macrophages of any species whereas the binding of living thymocytes was species specific. Living thymocytes attained maximum binding in approximately 1 hr and then the fraction bound gradually diminished. Formalin-treated thymocytes remained bound to the macrophage and appeared to be phagocytized. Released thymocytes did not bind to fresh macrophages, but released macrophages bound to fresh thymocytes. The results suggest that the binding of thymocytes to macrophages results in maturation of thymocytes.

Animals

Isolation and enumeration of peripheral blood monocytes.

Monocytes were isolated by counterflow contrifugation from human peripheral mononuclear cells obtained from whole blood by the Ficoll-Hypaque technique. Examination of volume spectra of the monocytes showed a bimodal distribution with peaks at 330 and 370 micron3. The upper peak contained 61.4 +/- 3.3% of the total monocyte population, whereas the remainder were in the lower peak which overlaps the lymphocyte spectrum. The purity of the monocyte preparations from six normal adult donors, identified by peroxisomes observed by electron microscopy, was 90.4 +/- 1.6%.

Adult

Effect of organ culture on the survival of thyroid allografts in mice.

Mouse thyroid can be maintained in organ culture for 4 weeks. Uncultured BALB/c thyroid is rejected 10-15 days after transplantation under the kidney capsule of H-2 disparate recipients (C57BL, CBA). Organ culture of thyroid tissue prior to transplantation prolongs allograft survival. This prolongation of graft survival increases with increasing time in culture and 80-90% of BALB/c thyroids maintained in culture for 26 days survive in allogeneic CBA recipients for a 60- to 70-day test period. These allografts show normal function as measured by 125I uptake, and show no histological evidence of chronic rejection. Cultured allografts can be rejected if the host's immune system is stimulated with viable leukocytes of donor origin. Host animals carrying a functioning allograft are not tolerant of donor tissues and will reject a second uncultured allograft from the same donor strain.

Animals

Comparative immunochemical studies of primate hemoglobins.

The antigenic properties of a number of chromatographically purified primate hemoglobins were compared to those of normal human hemoglobin using a sensitive radioimmunochemical procedure. The degree of inhibition of the antigen-antibody reaction with heterologous hemoglobins appeared to be related to the structural similarity of these proteins to the normal human hemoglobin immunogen. With the exception of the baboon hemoglobin, the antigenicity of the hemoglobins paralleled the phylogeny of the primates. The gorilla and chimpanzee hemoglobins were antigenically identical to normal human hemoglobin, whereas the gibbon and orangutan hemoglobins were substantially more variable. Of the Old World monkey hemoglobins examined, the baboon produced lower inhibition values, suggesting a greater degree of structural dissimilarity than other Cercopithecoidea hemoglobins, which is compatible with a greater rate of evolutionary change occurring in this protein. Using the known amino acid sequences of human and other primate hemoglobins, we have attempted to identify antigenic determinant areas of the proteins.

Alouatta

Is the macrophage the stimulating cell?

Using CAF1 spleen cells to stimulate parental strain BALB/c spleen cells in a mixed lymphocyte culture, column separation of responding cells increased their response whereas the same treatment of stimulating cells reduced their activity approximately 95 per cent. Peritoneal macrophages from CAF1 mice were found to stimulate BALB/c spleen cells poorly if present in comparable numbers or if they were cultured for 24 hours before adding responding cells. However, if the F1 macrophages were in contact with the BALB/c cells for only 4 hours, their stimulating effect was increased strikingly. Under these conditions BALB/c macrophages had no effect. It is concluded that the macrophage is probably the most effective stimulating cell and may be the only cell with this capability.

Animals

Inhibiton of tumor cell proliferation: second role for suppressor cells?

An antimitotic factor for mouse tumor cells was isolated from the supernatant fluids of antigen-stimulated ovalbumin-immune mouse spleen cells. A similar antimitotic factor was obtained from the supernatant fluids of phytohemagglutinin-stimulated non-immune spleen cells. The inhibitor prevented the multiplication of mouse L929 fibroblast cells in vitro and the in vivo proliferation of Ehrlich ascites tumor cells. Inhibition was not due to cytotoxic effects and the antimitotic effects were reversible. The antimitotic activity may be species-specific since the purified factor obtained from mouse spleen cells had no effect on human or monkey cell lines. This factor appears to be the same as the T lymphocyte-dependent suppressor for antibody production that we described previously. Several implications for the production of the suppressor in response to tumor cells that may be beneficial or harmful to the host are discussed.

Animals