Desensitization. V: Suppression of MIF production by lymphokine-activated macrophages

The systemic injection of high doses of antigen into a previously immunized animal results in a state of transient anergy with respect to cell-mediated immune reactions. This phenomenon is known as desensitization. We have previously shown that desensitization is a multistage process. The initial 24-hr period is characterized by excessive lymphokine production with a failure to express delayed hypersensitivity reactions due to abolition of local chemotactic gradients. Subsequent stages of desensitization involve failure of lymphokine production in vivo. The results presented here demonstrate that lymphocytes obtained from immunized and desensitized animals later than 24 hr after desensitization are markedly suppressed in their ability to produce MIF. In addition, it was found that lymphokine-activated macrophages can suppress in vitro MIF production by lymphocytes from immune, nondesensitized animals. In vitro and in vivo activation of macrophages were equally effective. Thus, it is likely that at least one mechanism for the inhibition of lymphokine production in the post-24-hr period of desensitization, involves activation of a population of suppressor macrophages by lymphokines produced during the initial 24-hr period.