1496 Suppression of Delayed Hypersensitivity

6-mercaptopurine (6-MP) ~ has been shown to suppress the expression of certain experimental and clinical immune responses. These include delayed cutaneous reactivity to antigen (1), allograft rejection (2), manifestations of certain "autoimmune" disorders (3), and some types of humoral antibody response (4). The mechanisms involved in these suppressive effects of 6-MP are still open to question. Evidence has been presented both for specific immunosuppressive (5) and nonspecific anti-inflammatory (6) actions. This study describes in vivo and in vitro functional studies in guinea pigs receiving 6-MP after presentation with Mycobacterium tuberculosis. This model was chosen to study the effect of 6-MP upon developing cellular immunity after preimmunization, the situation most analogous to the conditions of clinical use. Specific attention was paid to the two major cell type populations known to be important in the manifestations of delayed hypersensitivity, the lymphocytes and monocytes-macrophages (7). Sequential comparative measurements in vivo were made of: (a) patterns of skin test reactivity to tuberculin, irritants, and certain vasoactive substances; (b) patterns in levels of circulating leukocytes; (c) transfer studies involving specific subpopulations of cells; (d) several quantitative in vitro measurements of lymphocyte and monocyte reactivities, such as: (i) lymphocyte blast cell transformation and proliferation in response to tuberculin or phytohemagglutinin; (ii) macrophage inhibition factor (MIF) activity production; (iii) macrophage function.