Impact of Tax on Dendritic Cell Immunologic Function

Pennsylvania State Univ Hershey Med Ctr, Hershey PA

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Abstract

DESCRIPTION (provided by applicant): Human T cell leukemia virus type I (HTLV-I) is the etiologic agent of both adult T cell leukemia (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAMKSP). Although the genesis of HAM/TSP likely involves several steps, the generation of a highly specific and effective population of Tax-specific CD8+ cytotoxic T lymphocytes (CTLs) that migrate to the central nervous system (CNS) is of central importance in the genesis of neurologic disease. Presentation of antigenic Tax peptides by mature dendritic cells (DCs) to CD8+ T cells likely plays an important role in the induction of a Tax-specific CTL response. The central hypothesis of the proposed studies is that Tax induces functional alterations in DCs causing their maturation and activation, thus increasing the efficiency of CDS+ T cell activation and leading to the generation of a highly reactive Tax-specific CTL compartment that participates in the genesis of HAM/TSP. The specific aims of the study are to examine the (1) effect of Tax on the activation of murine dendritic cells and primary human peripheral blood-derived dendritic cells; (2) effect of Tax on the immunologic function of murine dendritic cells and primary human peripheral blood-derived dendritic cells; and (3) the pathway and mechanism by which Tax induces dendritic cell maturation.