Statistics in cellular typing.
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Biomedical subjects
Publications and source records attributed to D Franks.
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Human normal lymph nodes, irrespective of their anatomical site of origin, have a low K cell activity, which may not be detected except with the appropriate target cell and at high lymphocyte to target cell ratios (100:1). This very low killer cell activity is also found in all the homolateral axillary nodes of patients with clinical stage I and II carcinoma of the breast and in the regional draining nodes of a variety of solid tumours, whether small and localized or large and with extensive spread. In all cases proximity to the tumour and obious hyperplastic changes in the nodes have no modifying effect. This pattern of minimal reactivity is similarly found with tonsillar lymphocytes and with nodes draining inflammatory foci. The Fc and C3 receptors on surface membranes are dectected with ease, and pretreatment of lymphocytes by incubation, washing and enzymatic treatment fail to alter their reactivity, thus excluding effector cell inhibition by immune complexes. The killer cell activity of lymphocytes from the blood of breast tumor patients is similar to the activity of lymphocytes from healthy controls.
The human non-allergized K (killer) lymphocyte has been characterized using selective depletion and isolation procedures based on surface markers. It was found to be a non-thymus-dependent, Fc-receptor-bearing cell. In an area which is controversial, our findings also indicate that the cell has immunoglobulin on its surface but lacks the receptor for the C3 component of complement (mouse). This would suggest it to be an (Fc + C3-) B lymphocyte.
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Normal human blood lymphocytes with affinity for ox red cells sensitized with IgG antibody, for normal or papain-treated sheep red cells and for ox red cells coated with mouse complement were used for rosette formation and the rosetting cells separated by density gradient centrifugation on Ficoll/hypaque. The non-rosetting cells at the interface were collected and compared with cell suspensions before treatment for direct and antibody-dependent cytotoxicity of human target cells. Depletion of Fc-receptor-bearing lymphocytes strongly decreased antibody-dependent cell-mediated cytotoxicity; reduction in the number (or depletion) of T cells and cells with C'3 receptor had no effect, showing the same or enhanced K-cell activity. It is concluded that one type of K or killer cell has Fc receptors but lacks C'3 receptors.
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The effect of prednisolone on the kinetics of killing of Detroit-6 cells by rat lymphocytes has been studied utilizing the release of 51Cr as a measure of target cell death. The results show that in both killing by allergized lymphocytes, and killing of antibody coated target cells by normal lymphocytes, there is a short (less than 15 min) prednisolone-sensitive induction phase. Prednisolone has no effect on the reaction after this phase. The inhibition of induction by prednisolone appears to have two mechanisms. The first occurs rapidly following the addition of the drug to the cells, and must involve a primary action of prednisolone. Washing the cells free of prednisolone allows initiation, and killing can proceed almost normally, but if these washed cells are preincubated before mixing with target cells, then a secondary inhibition of induction develops progressively.
Differences can be demonstrated between the lysis of xenogeneic target cells by lymphocytes of injected rats, which is inhibited by antiglobulin serum, and the lysis of antibody-coated xenogeneic target cells by normal rat lymphoid cells, which is much less readily inhibited. This difference is demonstrated by the dilution of antiglobulin which is effective, and by the fact that inhibition of lysis produced by allergic lymphocytes can be shown if the lymphocytes are treated with antiglobulin and then washed. Differences can also be shown in the time course of inhibition, since to be effective antiglobulin must be present at the time of mixing normal lymphocytes and antibody-coated target cells, whereas addition of antiglobulin to allergized lymphocytes 4 h ater mixing with target cells still produces significant inhibition. These results are compatible with the hypothesis that allergic lymphocytes have immunoglobulin on their surfaces and kill by a different mechanism from the lymphoid cells which lyse antibody-coated target cells.
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