CHARACTERIZATION OF EXPERIMENTAL LEPROSY

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We have shown mangabey monkeys (Cecocebus atys atys) to be a model for the study of experimental leprosy. Rhesus (Macaca mulatta) and African green (Cercopithecus aethiops) monkeys show promise of also being susceptible to leprosy. The goals of this proposal are: 1) to continue to study clinically, immunologically and histopathologically untreated and treated mangabeys, rhesus and African green monkeys to further define the course of leprosy; 2) to inoculate additional rhesus and green monkeys to define their susceptibility to experimental leprosy; 3) to study the effects of immunomodulators (thymopoietin, interleukin 2, gamma-interferon, BCG + killed Mycobacterium leprae and possibly transfer factor); 4) to define the relationship of lepromin skin testing to the susceptibility to and course of leprosy in monkeys; 5) to further characterize the mechanism of immune suppression that we have observed in mangabeys with leprosy; 6) to determine if mangabeys can be protected by vaccination with M. leprae antigens against challenge with live M. leprae; and 7) to maintain the established YRPRC mangabey breeding colony to provide animals for leprosy research. Animals will be monitored longitudinally, as we have been doing, before and after vaccination or inoculation or treatment. We will completely characterize animals prior to and at intervals after vaccination and after M. leprae inoculation, and during therapy. Studies will include: serum chemistries and hemograms; physical, clinical and neurological exams; nerve conduction velocities; bacteriologic, histopathologic and immunohistologic examinations of biopsies. Immunologic parameters to be studied are: in vitro mitogen and antigen (e.g., lepromin) responses of lymphocytes (L); in vitro L immunoglobulin (Ig) production; B- and T-L numbers and subpopulations; suppressor/helper T-L activity; natural killer (NK) cell cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC); blood mononuclear cell cyclic-AMP, phosphodiesterase and adenyl cyclase levels; lepromin skin test responses; serum levels of Ig's, C3, C4, immune complexes, prostaglandins, sialic acid, rheumatoid factor, and anti-M. leprae antibody. These studies will further define the susceptibility of monkeys to leprosy; further illuminate the course of leprosy in monkeys; show whether immunotherapy can alter the course of leprosy; and determine whether vaccination may offer protection against experimental leprosy transmission in monkeys.