RES blockade: effects on immunity and tolerance.

Reticuloendothelial cell blockade has been studied for decades in regards to physiological and immunological effects. "Overloading" of RE cells with inert colloidal particles, such as carbon or other particulate substances, has often been used to analyze the role of phagocytic activities in antibody formation, often with contrasting results. In the present studies the effects of colloidal carbon treatment of mice on immunologic responsiveness to sheep erythrocytes was investigated. Pre-treatment of mice with carbon shortly before either primary or secondary immunization with SRBCs markedly suppressed the expected antibody response, as shown by depressed numbers of hemolytic antibody plaque forming cells. Carbon treatment did not affect antibody forming cells per se as shown by lack of an effect on plaque forming cells when carbon was given after SRBCs, either in vivo or in vitro. Carbon injection before primary immunization prevented development of "immunologic memory," as shown by an altered secondary immune response. Mice given carbon and SRBC several weeks before secondary immunization with RBCs developed a primary type antibody response characterized by appearance of 19S antibody with little or no 7S hemolysins, characteristic of a secondary response. Furthermore, by appropriate treatment of mice with carbon and SRBC, immunologic unresponsiveness to SRBCs could also be induced, as evident by absence of both 19S and 7S antibody formation after subsequent challenge immunization with sheep erythrocytes. The mechanisms involved in RE "blockade" induced aberrations of normal immune responses may be related to effects on macrophages or soluble humoral factors, or both. It is unlikely that carbon treatment affects immunocytes directly. Further studies concerning the nature and mechanism of RE blockade on cellular and humoral components of the immune response mechanisms seem warranted and should provide more insight concerning the role of macrophages in antibody formation.