Human T-cell leukemia virus type I Tax induces the expression of dendritic cell markers associated with maturation and activation

Abstract

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 (HAM/TSP). 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 pivotal importance in this neuropathologic process. Presentation of Tax peptides by activated dendritic cells (DCs) to naive CD8+ T cells likely plays an important role in the induction of a Tax-specific CTL response and the eventual neurologic dysfunction observed in HAM/TSP. The immune response mounted during HTLV-I infection is primarily targeted against Tax with both Tax-specific antibodies and CTLs found in HTLV-I-infected individuals, indicating that Tax is available for immune recognition. Studies have suggested that Tax may be secreted from HTLV-I-infected cells and act as an extracellular cytokine, be internalized and processed for presentation, or be transported to the nucleus where it may act as a transcriptional activator. The authors report in this article that purified Tax induces DC activation involving an increase in the production of CD80 and CD86 mRNA in the absence of corresponding protein synthesis. Furthermore, intracellular Tax down-regulates the protein expression of molecules involved in antigen presentation. This implies a difference in the mechanism of Tax activity depending upon its location. Additionally, treatment of JAWS II DCs with extracellular Tax decreases the ability of DCs to present a major histocompatibility complex (MHC) class I-restricted peptide, indicating that Tax likely matures the DCs to the point where presentation of a secondary antigen is restricted. The implication of the experimental results with respect to the generation of a Tax-specific CTL compartment that participates in the genesis of HAM/TSP is discussed.