Development of mitogen responding T cells and natural killer cells in the human fetus.
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Biomedical subjects
Publications and source records attributed to O Lassila.
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We describe an 8-year-old girl who presented a massive mediastinal tumour of thymic origin. Surgical excision was unsuccessful. Irradiation treatment (4,500 rad) together with intensive combination chemotherapy resulted in regression of the tumour. After three months, an increase of blasts was observed in the peripheral blood and bone marrow. The terminal phase was characterized by acute leukaemia, which did not respond to chemotherapy. Despite the thymic origin of this malignancy, the blast cells contained non-specific esterase activity as determined by naphthol-AS-acetate as substrate. The NaF-sensitive form of this enzyme is a characteristic of monocytes-macrophages. Other monocyte-macrophage markers were, however, negative. We conclude that the NaF-sensitive naphthol-AS-acetate esterase is not limited to tumours of the monocyte-macrophage system.
Open heart surgery is associated with a moderate to severe postoperative of cell-mediated immunity. To characterize this defect, T-suppressor lymphocytes were studied in nine patients undergoing elective aortic/mitral valve replacement surgery. A decrease of the number of T-suppressor lymphocytes was observed after the operation. At the same time the activity of concanavalin A (Con A)- and phytohaemagglutinin (PHA)-induced suppressor cells decrease. Thus the decrease of cell-mediated immunity after open heart surgery seems not to be due to activation of suppressor lymphocytes.
This report is a cytological and functional description of 3 cases of malignant histiocytosis (MH). These patients suffered from an intense proliferation of histiocytic cells that occurred predominantly in the bone marrow in 2 cases (the primitive cell type of MH), and in the spleen, liver and intraabdominal nodes in the third patient (the mature cell type of MH). The malignant cells carried the cytological markers typical for the monocyte-macrophage series, e.g., acid phosphatase, NaF-sensitive naphthol-AS-acetate esterase, acid alpha-naphthyl-acetate esterase, lysozyme, and also Fc-IgG-receptors and mouse C3-receptors. Their in vivo phagocytic activity was investigated by ultrastructural studies. In every case, the histiocytic cells phagocytosed Candida albicans in vitro. The proliferative histiocyte compartment differed from that of the mature cells, although these two cell compartments were morphologically indistinguishable in the primitive-cell-type cases of MH. Malignant histiocytes were capable of destroying phagocytosed fungi, but this ability was clearly inferior to that of the mature histiocytes in these 2 cases. The results revealed that most, if not all, monocyte-macrophage characteristics are present in the malignant cells in MH. Nevertheless, the morphological and clinical features seemed to be variable.
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Chromosomally marked cells from the 7-day intraembryonic mesenchyme were transplanted into 14-day-old irradiated chick embryos. At the age of 6 weeks donor-derived T and B lymphocytes were shown to be present in the thymus, spleen and bone marrow, indicating that cells in the 7-day intraembryonic mesenchyme are capable of developing into functional T and B lymphocytes. In addition to the sex chromosome marker, IgG allotype was used as a marker; the results demonstrate that cells from intraembryonic haemopoietic sites develop into mature IgG-producing cells. In similar experiments, the 7-day yolk sac also proved to contain lymphoid stem cells. Since lymphoid cell progenitors are not present in the 2-day yolk sac, as has been shown previously in the yolk sac-embryo chimaeras and since circulation is established from day 2 of incubation onwards, lymphoid stem cells present in the 7-day yolk sac are most likely secondary immigrants originating in the intraembryonic mesenchyme.
Two-day-old chick embryonic bodies were transplanted onto the area vasculosa of age-matched histocompatible blastoderms, resulting in the development of yolk sac-embryo chimaeras. Eighteen of these succeeded in hatching and became adults. Differences in the sex chromosomes and in IgG allotype between the embryo and the yolk sac were used to study the contribution of these two components to the lymphoid cell development. At 5-7 weeks of age the chimaeras proved to be completely normal in the IgM and IgG antibody production against human gamma globulin and Brucella abortus and in the lymphocyte responses to phytohaemagglutinin and concanavalin A. For the sex chromosome analyses bursa cells and specifically stimulated B and T lymphocytes were used. The latter was achieved by stimulating thymus, spleen, and bone marrow cells in vitro with anti-Ig and Con A. Only four out of 1498 mitoses analysed belonged to the sex opposite to that of the bird. Among the chimaeras eleven were marked through IgG allotypes. At the age of 3-20 weeks all eleven chimaeras showed serum IgG of the embryo allotype and none of the yolk sac type. These results, based on the use of two different markers, indicate that lymphoid stem cells in the chicken are originally derived from an intraembryonic source and not from the yolk sac.
The mitogenic responses of chicken peripheral blood lymphocytes were compared in two partially inbred chicken lines and in their hybrids. The lymphocytes of line P chickens showed a higher phytohaemagglutinin (PHA) response than those of line V chickens and (P X V)F1 hybrids. The Con A responses were of the same magnitude in all chicken lines. The higher PHA response in line P chickens was not sex-linked, apparently was not associated with the major histocompatibility complex and it did not correlate with immunoglobulin G allotypes.
A 45-year-old female developed blastic metamorphosis in chronic granulocytic leukaemia after 52 months of chronic phase. During the subsequent 6--7 months, lymphosarcomatous enlargements of various lymph nodes developed. The blast cells in lymph nodes differed morphologically from those in bone marrow and blood, being 'lymphoid' non-B, non-T, non-ALL cells. The karyotype of all metaphases from one lymph node was 47,XX, +21(Ph1+) being identical to the karyotype of medullary cells. However, the karyotype of all blasts from another lymph node was 47,XX,+mar(Ph1+). It is likely that the local micro-environment controlled the clonal differentiation of these subpopulations which had originated from the same Ph1-positive multipotent stem cell. In lymph nodes and other extramedullary sites blasts were primitive without differentiation, but a myeloid differentiation in the bone marrow was demonstrated morphologically and cytochemically.
The effect of levamisole in vivo was studied on the PHA and Con A responses of chicken peripheral blood lymphocytes and on the in vivo antibody response to a thymus dependent antigen (BSA) and to a thymus independent antigen (Brucella abortus). Levamisole (0.25 mg/kg) increased significantly both the PHA and Con A responses of chicken blood lymphocytes. The antigens were given at the time of enhanced mitogenic responses and a significant increase was observed in both IgM and IgG antibodies to BSA. In contrast, no effect was obtained on antibody responses to Brucella abortus organisms. The results show that levamisole is able to enhance both humoral and cellular immune responses in normal chickens. The effect is probably mediated by the activation of the T cell function and effects only antibody responses to thymus dependent antigen. These findings confirm and extend the observations regarding the ability of levamisole to modulate immune responses.
In order to study the bursal origin of T cells, 18-d chromosomally-marked bursa cells were transplanted into 18-d chick embryos treated with cyclophosphamide (CY). Transfer of bursa cells restored not only the humoral immune functions but also the mitogenic responses of peripheral blood lymphocytes against phytohaemagglutinin and concanavalin A (Con A). Transplanted bursa cells proliferated primarily in the recipients' bursa. Only 8 out of 209 Con A responsive spleen cells were of donor origin, but no donor-derived cells were observed in the thymus. These findings suggest that cells in the 18-d embryonic bursa are already committed to the B cell lineage, and are not capable of migrating into thymus and of developing into mature T cells.
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Cyclophosphamide-treated 18-day-old chick embryos were transplanted with cells from 7-day intraembryonic mesenchyme; the recipients and donors were identical at the major histocompatibility locus. At the age of 35 days, the cell recipients were studied to determine the reconstitution capacity of the transplanted cells. The transplantation resulted in a complete restoration of IgM and IgG class antibody production against human gammaglobulin and Brucella abortus, and of microscopic morphology of the bursa of Fabricius and of the germinal center formation in the spleen. These findings demonstrate that 7-day intraembryonic mesenchyme of the chick embryo harbor prebursal stem cells. These findings confirm our previous observations in the yolk sac-embryo chimeras indicating that lymphoid stem cells originate in the intraembryonic hematopoietic sites.
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The effect of a single halothane anaesthesia on the secondary antibody response and the lymphocyte response in vitro to phytohaemagglutinin (PHA) and concanavalin A(Con A) was studied. The antigens used were bovine serum albumin (BSA) and killed Brucella abortus organisms (Brucella). IgG and IgM antibodies against these antigens were quantified by solid-phase radioimmunoassay. Lymphocyte transformation was studied by a whole blood micromethod. The chickens were anaesthetised for two hours with 2% v/v halothane. The halothane concentration of the blood was measured by gas chromatography at the end of the anaesthesia. Halothane anaesthesia had no effect on the secondary antibody response against BSA and Brucella. In contrast, it caused a significant decrease in the lymphocyte response to PHA and Con A. This suppression was transient, however, and full recovery of the lymphocyte function was observed by the first day after anaesthesia.