Immunosuppressive effect of cyclosporin A on Mycobacterium bovis BCG infections in mice

Abstract

The effect of increasing doses of cyclosporin A (CsA) given to mice infected intravenously with Mycobacterium bovis BCG was investigated. Development of both tuberculin hypersensitivity and acquired antituberculous resistance was suppressed in a dose-responsive manner. Daily dosages at 100 mg/kg of body weight prevented any reduction in the BCG counts within the lungs, liver, or spleen. This effect was associated with lowered nonspecific resistance to a Listeria monocytogenes challenge and a decline in specific protective immunity adoptively transferred to naive recipients. CsA treatment had no effect on antilisterial activity by activated macrophages or on the antituberculous immunity expressed by specific memory T cells. CsA treatment inhibited the ability of BCG-vaccinated mice to produce gamma interferon (IFN-gamma) after a secondary stimulation with live BCG or with lipopolysaccharide. Spleen cells from BCG-infected mice which were exposed to daily treatment with CsA showed reduced IFN-gamma production in response to purified protein derivative or concanavalin A stimulation, suggesting that the immunosuppressive effect of CsA on BCG-infected mice was expressed by inhibiting the development of effector T cells responsible for the production of IFN-gamma.