The ability to produce delayed type hypersensitivity (DTH) reactions in both humans and animals correlates well with the integrity of T cell mediated immunity. In clinical conditions where the capacity to produce DTH reactions is lost (Anergy), disordered immunoregulation at the level of the T lymphocyte is suspected. Anergy frequently accompanies granulamatous diseases such as sarcoidosis. Activated macrophages and T lymphocytes are required to produce a granulomatous reaction. The subpopulation of T cells involved in the generation of this destructive lesion is unknown. It is also unclear whether macrophages or lymphocytes take the primary role in initiating the inflammatory response. We hypothesize that lymphokines released by suppressor lymphocytes activate a specific subclass of macrophages to produce this unique inflammatory response. Activated macrophages in sarcoidosis secrete large amounts of Angiotensin-converting enzyme (ACE). We plan to examine mononuclear cells obtained by bronchial alveolar lavage from both control subjects and those with sarcoidosis. We will examine the phenotypic heterogeneity of the mononuclear cells present and relate this to the function of harvested cells. We will analyze, in vitro, the ability of lymphocytes and macrophages from patients with sarcoidosis to modify the performance of normal T lymphocytes and macrophages. In addition the immuno-modulating capacity of ACE will be examined. Kveim antigen, an extract from the spleen of patients with sarcoidosis, will be studied for its ability to stimulate suppressor T lymphocytes. Guinea pigs can be made anergic by """"""""desensitization"""""""". Large amounts of antigen injected into highly sensitized animals produce a dimunition rather than an increase in their capacity to produce DTH. Anergy appears to be mediated by cyclophosphamide sensitive suppressor T lymphocytes although the role of the macrophage has not been delineated. We will attempt to produce BCG granulomas in normal and cyclophosphamide treated guinea pigs. Adoptive transfer experiments with specific subclasses of T cells and macrophages will be performed to clarify the mechanisms causing anergy. We are developing an isotope dilution technique using Indium III labeled T lymphocytes to study T lymphcyte migration and T cell mass.
| Rankin, J A; Huang, S S; Sostman, H D et al. (1991) An analysis of the inter-relationships among multiple bronchoalveolar lavage and serum determinations, physiologic tests, and clinical disease activity in patients with sarcoidosis. Sarcoidosis 8:19-28 |
