Suppressor T cells in cell-mediated immunity.
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Biomedical subjects
Publications and source records attributed to M Zembala.
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The lymph node and spleen cells of mice painted on the skin with the contact sensitizing agent, picryl chloride, transfer contact sensitivity. Their ability to transfer reaches a peak 4 days after immunization and is absent by day 6 providing the recipient mice are challenged shortly after transfer (Chase type transfer). In contrast, when challenge of the recipients is delayed for 6 days (adoptive transfer), lymph node and spleen cells show the greatest ability to transfer 8-12 days after immunization. When cells taken 4 days after immunization (which transfer contact sensitivity) are mixed with cells taken at 6-11 days (which fail to transfer), the mixture shows little ability to transfer. This provides evidence for the occurrence of suppressor cells. Lymph node and spleen, and thymus cells show suppressor activity. The suppression is specific and cells from donors immunized with the contact-sensitizing agent oxazolone will not suppress passive transfer of contuse of the loss of ability of lymph node and spleen cells in transfer later than day 6 after immunization. Experiments on the loss of radioactivity from lymph nodes labelled with 125I-iododeoxyuridine (IUDR) suggest that loss of cells from the lymph nodes may be a contributory factor.
Contact sensitivity was produced in mice by painting the skin with picryl chloride and was assessed by the increase in ear thickness following local challenge. Contact sensitivity was passively transferred by immune lymph node and spleen cells taken at 4 days. The mice were then challenged immediately and the reactions read at 24 and 48 hr. Immune lymph node and spleen cells taken at day 8 virtually fail to transfer. Experiment showed that they contain cells which suppress passive transfer. These are demonstrated by mixing approximately equal numbers of 4-day cells, which transfer contact sensitivity, and cells taken at later times and injecting them intravenously into recipients. These 'suppressor cells' can be demonstrated by day 6 and are still present at day 11 after immunization. The precursors of the suppressor cells are sensitive to cyclophosphamide. Irradiation of immune mice 2 days before taking cells also selectively inactivates the suppressor cells. When mice are pretreated with cyclophosphamide before immunization or irradiated 2 days before transfer, the lymph node and spleen cells taken on day 9 after immunization transfer contact sensitivity. In contrast the same number of cells from untreated mice were inactive. This suggests that the cells which mediate passive transfer or their precursors may occur in an inhibited form in lymph nodes and spleen at later times after immunization. These suppressor cells in immune mice differ from the T suppressor cells produced by the injection of picryl sulphonic acid--an agent which causes unresponsiveness: (1) the precursors of the T suppressor cells resist cyclophosphamide; (2) the T suppressor cells are found in mice treated so as to produce unresponsiveness while the other type of suppressor cells occurs in mice immunized for contact sensitivity. However, both types of suppressor cells are selectively inactivated by irradiation as compared with the cells which mediate contact sensitivity and both are able to act on the effector stage of contact sensitivity.
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The respiration rate, aerobic glycolysis and glycolytic enzyme activities of purified mouse peritoneal macrophages increase during phagocytosis of either free or antibody-coated SRBC. These changes, however, seem to be roughly parallel to the amount of phagocytized antigen. In the digestive phase, Ag-Ab complexes induce more marked changes in macrophage metabolism than a comparable amount of free antigen. Lactate production, activity of several glycolytic enzymes and alanine-aminotransferase as well as glycogen content are greatly affected. Since in cell transfer experiments macrophage-associated SRBC can prime normal recipients for antibody response, whereas cell-associated SRBC-antibody complexes cannot, it is concluded that the changed macrophage metabolism drives antibody-coated antigen into metabolic channels allowing its rapid and total degradation.
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