Richard M. Locksley, M.D.
University of California, San Francisco

Optimizing Immunity to Complex Pathogens In Vivo.

This research involves mechanisms that lead to secretion of certain types of molecules, termed cytokines, that activated lymphocytes make in mediating protective immunity. Funding from the Ellison Medical Foundation will enable the establishment of mice engineered to express genetically marked cytokine genes that allow activated cells to be identified rapidly in a manner that keeps them alive for further study. In this way, T cells that mediate protective immunity to an array of pathogens, including protozoa like Leishmania, intestinal worms and bacteria such as the organism that causes tuberculosis, will be analyzed in order to characterize markers displayed by protective T cells. Vaccines can then be evaluated by their capacity to establish similar characteristics as those identified in protective T cells that arise after natural infection. Such studies will prove useful not only in characterizing the production of protective T cells after natural infection, but in providing a system for the surrogate evaluation of vaccine efficacy.

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