INTERLEUKIN-2 INDUCED ANTI-FUNGAL ACTIVITY

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Fungal infections in general and Candida albicans infections in particular are important causes of morbidity and mortality in immunocompromised individuals. This study will evaluate a novel means by which to limit the development of fungal infections caused by Candida albicans. It has been very difficult to understand the means by which the mammalian host deals with limiting the growth of fungal hyphae, that reach lengths of 40-60 um, in vivo. Activated lymphocytes may influence the growth of fungal hyphae. If true, then such activated lymphocytes may provide an important host defense mechanism by which fungi may be limited. Such a form of anti-fungal defense may be important when normal host defense mechanisms are disrupted or as an adjunct to other anti-fungal mechanisms in the normal host. It is the purpose of this investigation to clearly identify the immunological nature and the functional activity of such an activated lymphocyte population. This identification will permit a direct assessment of the potential biological activity of the activated lymphocyte population and will lead to a clearer understanding of the mammalian host protective response to Candida, albicans. These observations are important since during the last two decades the incidence of fungal infections in general and Candida albicans infections in particular have increased markedly. Hematogenously disseminated Candida albicans infections have become increasingly significant in patients with; solid tumors, hematological malignancies, solid organ transplants, and in patients undergoing chemotherapy and in intensive care units. Candida albicans attributable mortality is high with the emergence of increasingly severe fungal diseases. Candida albicans has an occult presentation and is not only difficult to diagnose but are also difficult to treat. This investigation will determine whether interleukin-2 activated lymphocytes participate in and correlate with enhanced anti-fungal activity. The objectives of this project are to; 1) determine optimal growth and culture conditions for the interleukin-2 induction of maximal anti-fungal activity, 2) identify the functional and phenotypic characteristic of the anti-fungal lymphocytes, 3) clarify the mechanism of anti-fungal activity and 4) determine the effect of interleukin-2 induced lymphocytes on the survival rate of mice with experimental Candida albicans infections. This investigation will serve as an important experimental step in the analysis of the host protective response to the hyphal form of Candida albicans and will lead to a more complete understanding of the role of lymphocytes in the protection of immunocompromised individuals infected with fungi.