CLONAL ANALYSIS OF LUNG AND BLOOD T-CELLS IN PATIENTS WITH SARCOIDOSIS

Background - Sarcoidosis is a disease characterised by clinical ''aner gy'' to delayed type hypersensitivity antigens and the formation of no n-caseating granulomas, which frequently manifests in the lungs as a T lymphocyte/mononuclear cell alveolitis. Although there is an increase d proportion of T cells in bronchoalveolar lavage (BAL) samples from t hese patients, and these T cells often show evidence of activation and spontaneous secretion of cytokines such as interleukin 2 (IL-2) and i nterferon gamma (IFN gamma) - a pattern similar to delayed type hypers ensitivity reactions it is unclear whether both cytokines are produced by the majority of T cells derived from the lungs of patients with sa rcoidosis or whether unique subpopulations of T cells produce each cyt okine. In this study the properties of T cells cloned from BAL fluid s amples of patients with sarcoidosis have been analysed. Methods - T ce lls were cloned by limiting dilution using IL-2, phytohaemagglutinin, and irradiated feeder cells. Cloning efficiencies were compared and ph ytohaemagglutinin induced clonal production of IL-2, IFN gamma, and IL -4 was determined by bioassay (IL-2 and IFN gamma) or ELISA (IL-4). Re sults - T cells derived from the BAL fluid of patients with sarcoidosi s cloned less efficiently than those from blood of the same individual s. Lung derived clones (CD4+ or CD8+) produced IFN gamma more frequent ly and to a higher titre than blood derived clones, whereas IL-2 produ ction by CD4+ clones derived from BAL fluid was less than that from bl ood derived clones. Interestingly, IL-4 production by clones from both sites was similar. Analysis of the coproduction of IL-2, IFN gamma, a nd IL-4 by these BAL fluid clones did not demonstrate a predominant '' Th1''-like population which has been suggested to underlie delayed typ e hypersensitivity reactions. Conclusions - The reduced cloning effici ency of T cells from the lung compared with the blood in sarcoidosis i s consistent with, although probably more pronounced than, previous ob servations in normal lungs and shows that T cell hyporesponsiveness is not overcome in the lungs of patients with sarcoidosis. Furthermore, major differences exist between the cytokine producing potential of T cells derived from the lung and the blood in sarcoidosis, and these pa rallel the differences in the properties of blood and lung T cells see n in healthy individuals.