Enhancement of DTH reaction and inhibition of the expression of class II transplantation antigens by in vivo treatment with antibodies against gamma-interferon.

During the delayed type of hypersensitivity (DTH) reaction in the skin, class II transplantation antigens are expressed on the keratinocytes. This induction is attributed to the action of gamma-interferon (IFN-gamma). We have now studied the influence of antibodies against IFN-gamma on the DTH-reaction. Lewis rats were sensitized to 2,4-dinitro-1-fluorobenzene (DNFB) and challenged 5 days later with DNFB on the ears. Immediately before challenge each animal in one group (n = 16) was given 1 mg of mouse monoclonal antibodies (MoAb) against rats IFN-gamma, denoted DB-1, intraperitoneally (i.p.), another group (n = 15), 1 mg of an irrelevant MoAb and a third group (n = 11) was left untreated. The ear thickness was measured with a micrometer, before challenge and after 24, 48 and 72 h. At 72 h all rats were killed, the ears cut off, snap frozen and stained with immunoperoxidase using MoAbs OX 6 and OX 17, directed against rat class II antigens. The DB-1 treated group was found to have a larger ear swelling that was statistically significant at each time point compared with the other two groups. Furthermore, the animals given DB-1 showed class II antigen expression on Langerhans' cells, but almost none on keratinocytes. In contrast, the rats in the two other groups displayed a moderate to strong expression of class II antigens on keratinocytes as well as on Langerhans' cells. It is concluded that DB-1 can inhibit class II antigen expression on keratinocytes during the DTH- reaction and also enhance the local response.