Limiting dilution analysis of the specificity of influenza-immune cytotoxic T cells.
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Biomedical subjects
M Allouche
Publications and source records attributed to M Allouche.
Limit-dilution analysis of weak influenza-immune T cell responses associated with H-2Kb and H-2Db.
A limiting-dilution analysis has been made of influenza-immune cytotoxic T lymphocyte (CTL) response patterns associated with H-2Kb and H-2Dd in the B10.A(5R), and H-2Kk and H-2Db in the B10.A(2R) and B10.A(4R) recombinant mouse strains. In previous in vivo experiments the H-2Kb allele has been shown to be associated with low responsiveness or nonresponsiveness, whereas Db-restricted influenza-specific responses were found to be weak in recombinant strains that possessed the Kk allele. Influenza-immune CTL restricted to the more "dominant" H-2Dd and H-2Kk alleles were found consistently when primed T cells were restimulated in vitro under limiting-dilution conditions. Precursors were present at frequencies of at least twice background levels (lysis of normal targets) in the great majority of experiments, performed with or without added helper factors. The H-2Kb- and H-2Db-restricted responses were much more variable and, for H-2Kb but not for H-2Db, were completely absent when the culture medium did not contain added interleukin preparations. Even so, experiments in which individual microcultures were tested on more than one target demonstrated conclusively both that H-2Kb-restricted CTL can be generated under limiting-dilution conditions and that most, if not all, of these T cells do not cross-react with influenza virus presented in the context of H-2Dd. The characteristics of these "weak" responses are thus that they are more help dependent and show evidence of greater variability between individual mice than the "dominant" CTL clones do.
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Malignant bone tumours induced by a local injection of colloidal radioactive 144Cerium in rats as a model for human osteosarcomas.
Lung metastases were observed in 80% to 85% of rats bearing advanced malignant bone tumours (osteogenic osteosarcomas and angiosarcomas). These tumours were induced in 2-month-old Sprague-Dawley rats by inoculation of a colloidal suspension of radioactive cerium (144Ce) into the hind leg, in close contact to the bones of the knee joint. Twenty-eight rats were killed or died spontaneously shortly after detection of palpable tumours at the site of injection: the incidence of lung metastases was 73.3% and 53.8%, respectively, for osteogenic sarcomas and angiosarcomas, showing that most lung metastases are present at the time of diagnosis of the primary tumour. Tumour-cell kinetic parameters were studied in 49 rats bearing tumours following intraperitoneal injection of [3H]thymidine. The labelling index (LI) of the primary tumours was significantly lower in advanced tumours (7.2% for osteosarcomas and 10.1% for angiosarcomas) than than in tumors examined at the time of detection (12.2% and 13.5%, respectively). Mitotic indices (MI) of all tumours were less than 1%. From the curve of the percentage of labelled mitoses (PLM) at different times after [3H]thymidine injection, Ts (6.5 h) and TG2 (1.75 h) were determined. TC and TG1 were also evaluated (18 h and 9.25 h, respectively). These results show that malignant bone tumours induced in rats with 144Ce may be a good model for human osteosarcomas and may be useful in studying the numerous problems in the therapy of malignant bone tumours in man.
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Bone tumours induced in rats with radioactive cerium.
A technique is described for the induction of metastasizing bone tumours in rats by local inoculation of 144cerium. Bone sarcomas develop in 90% of the animals and 74% of these had lung metastases. The tumours can be easily cultured and maintained by serial transplantations. Preliminary data of clinical, histological and kinetic characteristics of these bone tumours are given.
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Influence of increased temperature on the inhibition of rat osteosarcoma cell multiplication "in vitro" by interferon.
Purified rat interferon preparations proved effective in inhibiting cell multiplication in a rat osteosarcoma cell line. A pronounced increase in the inhibitory activity was found with increasing temperature. At 39 degrees C 20 Interferon units/ml appeared to be cytotoxic whereas incubation of cells with 2,000 Interferon units/ml at 35 degrees C resulted in a cytostatic effect.
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Intense tumour-cell destruction by syngeneic mice: role of macrophages, complement activation and tumour-cell factors.
When injected i.p. and in large numbers (10(7)) into syngeneic mice, 125IUdR-labelled L1210 cells are rapidly destroyed in a small proportion of animals, while in the other animals the lysis is low. This bimodal distribution is clearly visible 24 h after cell injection. The intense lysis occurs in fewer animals when macrophage-derived lysosomal enzymes are inhibited by trypan blue and if the complement is depleted by high doses of cobra venom factor (CVF). The intense destruction occurs in more animals after adjuvant treatment, if the mice are latently contaminated, after a moderate production of C3b by low doses of CVF, or after the injection of a tumour-cell dialysate. The destruction seems to be the result of positive feedback reaction which involves at least macrophages and complement activation.
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