LYMPHOKINES, CELLULAR IMMUNITY, DELAYED HYPERSENSITIVITY

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The primary aim is to determine the interrelationship between: (1) cell-mediated immunity (CMI); (2) in vivo release of migration inhibitory factor (MIF) and/or interferon-gamma (IFN-gamma); and (3) delayed hypersensitivity. The studies will be carried out in two types of inbred mice: (1) those resistant to Candida albicans and Mycobacterium bovis (BCG), high responders (in the in vivo release of the two lymphokines, MIF and IFN), and good reactors in delayed hypersensitivity; and (2) those susceptible to infection with C. albicans, low responders in in vivo MIF, and poor reactors in delayed hypersensitivity. Experiments will be planned and run to isolate the messenger RNAs involved in the formation or development of the three aforementioned immunologic phenomena. The messenger RNA fractions coding for MIF or a related factor causing cell-mediated immunity will be purified. The cDNA will be prepared and the responsible gene(s) isolated by molecular cloning in E. coli. Such clones will then be used for the production of MIF of the factor(s) causing cell-mediated immunity. These purified factors will then be analyzed for their capacity to enhance CMI in the susceptible murine strains. The cells responsible for the formation of the lymphokines and for the development of cell-mediated immunity will be separated and characterized. Also the thymic peptides that enhance or suppress CMI will be determined and the particular cellular circuits that they effect will be analyzed. (HF)