EFFECT OF CYCLOPHOSPHAMIDE AND IRRADIATION ON CELLS WHICH SUPPRESS CONTACT SENSITIVITY IN MOUSE

  • 1 January 1976
    • journal article
    • research article
    • Vol. 23  (3) , 554-561
Abstract
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 h. Immune lymph node and spleen cells taken at day 8 virtually fail to transfer. They contain cells which suppress passive transfer. These are demonstrated by mixing approximately equal numbers of 4-day cells, which transfer contact senisitivity, and cells taken at later times and injecting them i.v. 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. The same number of cells from untreated mice were inactive. The cells which mediate passive transfer on 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 [thymus-derived] suppressor cells produced by the injection of picryl sulfonic acid (an agent which causes unresponsiveness). The precursors of the T suppressor cells resist cyclophosphamide. 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. Both types of suppressor cells are selectively inactivation by irradiated as compared with the cells which mediate contact sensitivity and both are able to act on the effector stage of contact sensitivity. The importance of these results to tumor immunology is discussed.