Selective suppression of granuloma formation and delayed hypersensitivity in rabbits

Abstract

The relationship between dermal delayed hypersensitivity (DH) and granulomatous hypersensitivity was studied in rabbits sensitized with killed mycobacteria. Specific antigen challenge of sensitized animals resulted in extensive pulmonary granulomatous inflammation and induced suppression of both dermal DH and dermal granuloma formation. Whereas suppression of DH was concomitant with pulmonary granuloma formation, as is the case in a number of granulomatous diseases, a causal relationship between the two did not exist. Both DH and dermal granulomatous hypersensitivity were significantly suppressed whether or not the antigen challenge was of a granulomagenic (particulate) or nongranulomagenic (soluble) form. The data presented indicate that granulomatous hypersensitivity and DH are selectively suppressed with regard to different anatomical sites.Numerous human diseases are accompanied by the development of epithelioid granulomas. Immune granulomas generally are regarded to be cell mediated, as demonstrated by the ability to transfer the state of granulomatous hypersensitivity with immune lymphoid cells but not with immune serum (1). Delayed hypersensitivity (DH) also has been demonstrated to be mediated by components of the cellular immune system and its products (11,26). A striking incongruity exists in that several disease states (including sarcoidosis, lepromatous leprosy, and systemic fungal infections) are characterized by suppressed DH reactivity during periods of extensive granulomatous inflammation. In contrast, granuloma formation as a consequence of pulmonary tuberculosis and tuberculoid leprosy generally is accompanied by positive skin test responsiveness. It is not apparent how one expression of the cell-mediated immune system is suppressed while another expression of the same system apparently remains unaffected.Short-term suppression of DH can be accomplished by administration of relatively large quantities of specific antigen to previously sensitized individuals. This phenomenon has been termed desensitization by Uhr and Pappenheimer (25). A correlate of desensitization apparently exists during the latter stages of some diseases such as lepromatous leprosy, where massive antigen release is accompanied by loss of skin test reactivity to lepromin (3,21). Numerous investigators have demonstrated that the ability to elicit antigen-specific granulomas is not affected during states of antigen-induced desensitization (2,9,27). These reports all have in common the fact that DH was assessed dermally, whereas granuloma formation was evaluated at a different anatomic site, e.g., the lungs.The purpose of this investigation was to determine the relationship between DH and granuloma formation at the same anatomical location in response to similar antigens. The experimental system used in the present study has been well characterized with respect to formation of pulmonary granulomas (9,16,18). The following study is unique in that granulomas are elicited not only within internal organs, but also dermally at the sit...

Diseases associated with immunosuppression.

“…More recently, the relationship between granuloma formation and delayed hypersensitivity was studied in our laboratory (51). The results of this study indicated that dermal delayed hypersensitivity and allergic granuloma formation in the skin are both suppressed in sensitized animals following systemic challenge with specific antigen.…”

“…Secondary immunodeficiency may be defined as a disorder affecting host defenses in *Department of Microbiology and Immunology, Bowman Gray School of Medicine, Winston-Salem, North Carolina 27103. February 1982 which the initiating factor arises outside of the immune system or is not restricted to immune elements. Secondary immune impairment occurs more frequently than primary immunodeficiency and commonly occurs in an older age group.…”