Animal experimental studies on chronic granulomatous inflammation and T-lymphocyte-system

Abstract

The presence of lymphocytes in chronic granulomatous inflammations is frequently thought to indicate that thymus-dependent cellular immune mechanisms are involved in the pathogenesis of such processes. Therefore, in the present studies, a model of a granulomatous heaptitis (induced by heat-inactivated group A streptococci) was used to determine whether liver granulomata, consisting of macrophages and lymphocytes, could also be evoked in neonatally thymectomized or in congenitally thymus-deficient nude mice. The morphological (light and electron microscopical, immunohistological) investigations were supplemented with selective determination of T- and B-lymphocyte function. The thymus-deficient mice, after injection of streptococci, developed liver granulomata that did differ neither quanlitatively nor quantitatively from those of control animals with thymus. Lymphocytes were found within the granulomata in both animal groups. There was no evidence for functional disorder of the RES in thymus-deficient mice; on the contrary, RES-activity seemed to be increased. Phagocytosis of streptococci, their intracellular breakdown and streptococcal antigen-degradation occurred as fast or faster in such animals. PHA- and LPS-stimulation of spleen lymphocytes indicated a considerable depletion of T-cells in neonatally thymectomized mice and a complete absence of T-cells in congenitally thymus-deficient nude mice. However, radioimmunological determination of antibodies to group A streptococcal carbohydrate revealed that both groups of experimental animals possessed functionally active B-cells. Therefore, the granulomatous hepatitis described here can be defined as a focal reaction of the liver RES with "B-lymphocyte trapping". Cellular immune mechanisms are not involved in the pathogenesis of these lesions.