Adjuvant and suppressor activity of the polycation protamine hydrochloride in the primary immune response of mice

The effect of protamine hydrochloride (PH), a polycation, on the primary immune response of mice to sheep red blood cells (SRBC) was studied. Like other adjuvants, PH enhances or depresses the immune response depending on the time of injection of PH in relation to the antigenic challenge. The suppressive effect of PH correlated with the appearance of "activated" macrophages in the peritoneal cavity. A second injection of PH together with antigen abolished this suppressive effect. Transfer of "activated" macrophages resulted in an enhanced immune response when antigen was administered at the time of transfer, and in a depressed response when the antigen was given 1 or 2 days after transfer. It is concluded that the duration of the influence of "activated" macrophages on T or B cells determines the subsequent immune reactivity. It is discussed that the basic mechanism of action of PH is its ability to release lysosomal enzymes from macrophages. The mechanism by which these enzymes amplify the immune response remains to be clarified.