ANTIGEN-DETECTION IN-VIVO AFTER IMMUNIZATION WITH DIFFERENT PRESENTATION FORMS OF RABIES VIRUS-ANTIGEN, II - CELLULAR, BUT NOT HUMORAL, SYSTEMIC IMMUNE-RESPONSES AGAINST RABIES VIRUS IMMUNE-STIMULATING COMPLEXES ARE MACROPHAGE DEPENDENT

In this paper we describe the effect of depletion of splenic macrophag es on the uptake, and immune response against, different formulations of rabies virus antigen. Splenic macrophages were removed by intraveno us injection with clodronate liposomes. beta-propiolacton inactivated rabies virus (RV-BPL) and immune-stimulating complexes (iscom) contain ing these antigens were given to macrophage-depleted and control mice. In the absence of phagocytic cells in the spleen, antigen is still tr apped in the red pulp and to a lesser extent in the peri-arteriolar ly mphocyte sheaths (PALS) for both antigen formulations. The localizatio n pattern in the main area of immune response induction, namely the fo llicles, was unaltered after macrophage depletion. Functionally, the d epletion of splenic and liver macrophages had no influence on the indu ction of specific antibody responses in both RV-BPL or RV-iscom immuni zed mice, even though the latter presentation form was clearly associa ted with specific localization in the marginal metallophillic macropha ges. In RV-BPL immunized mice, macrophage depletion had no influence o n proliferative T-cell responses. However, macrophage-depleted mice th at were immunized with RV-iscom showed a significant decrease in proli ferative T-cell responses. These results confirm existing ideas on the spleen as a physical filter rather than an induction site for humoral responses and shed new light on the efficient role of iscoms as antig en-presenting moieties in relation to their specific in vivo localizat ion patterns and partial macrophage dependency.