Experimental epithelioid cell granulomas, tubercle formation and immunological competence: an ultrastructural analysis

An ultrastructural study of the cells comprising tubercles in experimental mycobacterial granulomas in rats is presented. Tubercle formation was compared in: (1) primary infections due to BCG at 49 days, (2) reinfection with BCG at 7 days, 8 months after primary infection and (3) lesions due to preformed BCG/anti-BCG complexes in antibody excess in unprimed animals at 10 days. The most rapid elimination of antigen with resolution of the lesion in the reinfection lesions, was effected by the early recruitment of cells morphologically characteristic of activated macrophages and immature epithelioid cells. The next best performance was in the immune complex lesion which at its height was maintained by a roughly constant size due to promonocytes, monocytes, macrophages, activated macrophages and immature epithelioid cells accumulated at the site. True epithelioid cells were rare. The slowest rate of healing in the primary 49 day granulomas, was associated with the whole spectrum of mononuclear phagocyte series of cells. All granulomas were surrounded by a cuff of mixed lymphocytes, interdigitating cells and fibroblasts. The rapid resolution of the reinfection lesions appeared as a loosely compacted infiltration of cells which allowed intimate contact of lymphocytes and macrophages. This was distinct from the tightly compared and compartmentalised zones of lymphocytes and macrophages which inhibited contact in the most slowly resolving lesions. An intermediate arrangement was seen in the immune complex granuloma. Another factor which predisposed to rapid resolution was the high vascularity of the central region of the granulomas. In the slow resolving group vascularity was diminished and peripherally situated.