Modulation of epithelioid cell granuloma formation to apathogenic mycobacteria by cyclosporin A

Epithelioid cell granuloma (ECG) formation after subcutaneous injection of different strains of mycobacteria has been followed by light and electron microscopy. EC granulomas are found at 2 weeks after injection at the local site and in the regional lymph nodes. The cellular composition of the inflammatory exudate as well as the reaction pattern of the lymphoid tissue showed characteristic time dependent changes. Infection with various strains of mycobacteria, however, did not reveal significant differences with respect to ECG formation. Treatment with cyclosporin A (CS-A) prevented the formation of ECG and the development of caseating necrosis. Macrophages accumulated at the local site and in the regional lymph node and contained numerous mostly well-preserved mycobacteria. No generalization of the infection was found, however. These results strongly suggest that ECG formation in vivo is 1) a T lymphocyte dependent phenomenon and 2) that inhibition of T lymphocyte activation by CS-A prevented also harmful effects of the mycobacterial infection in our model. The relevance of these results with respect to granulomatous diseases are discussed.