One of the most distressing and potentially serious health problems recently discovered in American life is the Acquired Immune Deficiency Syndrome (AIDS). In the short span of less than 3 years after the initial recognition, many patients have been discovered to have this syndrome. The agonizing and grim facts of the seriousness of the disease and very high mortality prompted several concerned agencies and individuals to launch a serious battle against this malady. AIDS patients become increasingly susceptible to life threatening infections, caused by several opportunistic microorganisms, which do, at the most cause only benign infection processes in normal individuals. This application concerns the immunopathologic studies with one of these, M. intracellulare. Unlike the other opportunistic microorganisms, M. intracellulare can cause a refractory, disseminated type of disease in non-AIDS patients as well. Following the earlier leads obtained from our laboratories, the suitability of the Beige mutants of C57B1/6 mice as a possible experimental animal model for AIDs patients with M. intracellulare infections will be investigated. Other attributes of the Beige mice, besides the evidence of their increased susceptibility to this infection, are the absence of natural killer (NK) cells, and increased suppressor cells - features established to be common in AIDS patients. An important aspect in this study is to assess the role of immunosuppressive and recreational drugs, commonly used by the AIDS patients, on the pathogenesis of this organism in this animal model, as judged by in vivo bacterial multiplication and mortality. In order to further characterize and strengthen the claims of this model, specific investigations on the immunomodulation of the host by way of assessment of prostaglandin (PGE2) and synthesis with its consequent influence on Interleukin-2 (IL-2) and gamma interferon (IFN). Protective studies in animals using indomethacin (inhibitor or prostaglandin synthesis), IL-2 and IFN will also complement the results of clinical studies with these agents, already in progress in this country. Finally, specific experiments aimed at characterization and quantitation of the T subset (T helper (TH) and T suppressor (TS) cell) populations and the TH:TS cell ratios in this mouse model, following infection with M. intracellulare will add further insight into the pathobiology of this syndrome and strengthen the suitability of this model.
