(Taken directly from the application) In order to obtain a better understanding of the induced mucosal and systemic immune responses to both transgene and vector, the associated T cell subset responses which include CD4+, CD8+, alpha beta and gamma-delta T cells and mucosal antibody responses in the respiratory tract and systemic compartment will be analyzed in the Immunology Core. The activation of CD4+ T helper type 1 (Th1) cells for the induction of cell-mediated immunity (as manifested by delayed type hypersensitivity) which contribute to inflammation and antibody mediated immunity regulated by Th2-type helper cells will be analyzed in the respiratory tract and associated lymph nodes. The roles for key Th1 and Th2 cytokines like IFN-y and IL-4 for the induction of these two T helper cell subsets will be assessed by the use of cytokine gene disrupted (knockout) mice. This will contribute to our understanding of vector-specific immunity and may reveal pathways to specifically decrease these responses by the absence or over-expression of specific cytokines. In addition to Th1 and Th2 cells, it is also clear that gamma delta T cells can play an incompletely understood role in the mucosal immune response. Therefore, our studies in the Core will address their potential role in mucosal and systemic immunity to vector and transgene by assessing their contribution in normal and gamma delta TCR-deficient mice. This Immunology Core will provide state-of-the-art analyses of Th1- and Th2-type and CTL responses to various constructs developed by CF gene Therapy Core Center investigators and pilot projects. In so doing, we will help optimize the vector and transgene for effective therapy with minimum inflammation.
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