Suppression of contact sensitivity by T cells in the mouse. I. Demonstration that suppressor cells act on the effector stage of contact sensitivity; and their induction following in vitro exposure to antigen.

Abstract

Mice injected intravenously with picryl sulphonic acid (PSA) fail to show contact sensitivity when subsequently immunized and challenged with picryl chloride applied to the skin. The injection into normal recipients of lymph node (and to a lesser extent, spleen and bone marrow cells) from mice treated with PSA, depressed the contact sensitivity which otherwise followed immunization by picryl chloride applied to the skin. Experiments were designed to show the location of the block in the development of contact sensitivity. Lymph node cells from mice treated with PSA (‘suppressor cells’) blocked the effector stage of contact sensitivity. This was shown by taking advantage of the fact that contact sensitivity to picryl chloride can be transferred to normal recipients by lymph node cells from mice immunized with picryl chloride (immune lymph node cells). The contact sensitivity is detected by applying picryl chloride to the ears of the recipients and measuring the increase in thickness at 24 h. The addition of lymph node cells from mice treated with PSA (suppressor cells) to the immune lymph node cells limited passive transfer of contact sensitivity. Although suppressor cells limited passive transfer they had little or no ability to depress the DNA synthesis which occurs in draining lymph node following skin painting with picryl chloride. Lymph node cells from mice treated with PSA do not immediately develop the ability to limit the passive transfer of contact sensitivity. PSA was injected into normal mice and their lymph node cells taken at various times afterwards. These cells first depressed the passive transfer of contact sensitivity when taken at 4 days. In contrast, cells taken after one day depressed the development of contact sensitivity when injected into normal mice which were then sensitized with picryl chloride and challenged 6 days later. Both these activities were present at day 10 and were waning by day 14. The depression of contact sensitivity by suppressor cells was specific. Cells from mice treated with PSA did not depress contact sensitivity to ‘oxazolone’. Moreover, these cells failed to block the passive transfer of contact sensitivity to ‘oxazolone’ even when the recipients were challenged with a mixture of picryl chloride and ‘oxazolone’. Lymph node cells treated for 2 h in vitro with PSA also blocked the development of contact sensitivity. T cells were probably involved, as treatment with anti-theta antibody and complement before incubation with PSA abolished this effect. Thymus cells were ineffective unless they were treated with neuraminidase. The hypothesis was put forward that the injection of PSA gives rise to an immunological response which generates specific suppressor cells.