Role of Integrin Signaling Activation on the Development of Human T Cell Leukemia Virus-1 (HTLV-1)-Associated Myelopathy/Tropical Spastic Paraparesis: Its Relationship to HTLV-1-Infected CD4⁺T Cell Transmigrating Activity into the Tissues

Abstract

The main clinical feature of human T cell leukemia virus-1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is slowly progressive spastic paraparesis with bladder dysfunction. HAM/TSP is induced by chronic inflammation in the spinal cord, mainly the lower thoracic cord. A long-standing bystander mechanism, such as the destruction of surrounding tissues by the interaction between infiltrated Th1-like, HTLV-1-infected CD4 T cells and HTLV-1-specific CD8 cytotoxic T cells (CTL), is probably critical for the induction of chronic inflammation. Although the HTLV-1-infected CD4 T cells in HAM/TSP appear to play a crucial role in the initial pathogenesis of HAM/TSP, the exact mechanisms of how these cells acquire their function as the first responders in the pathogenesis of HAM/TSP still remain unresolved. Herein, we propose the importance of the activation of both outside-in signals from integrin signaling and inside-out signals for integrin signaling in the HTLV-1-infected CD4 T cells of HAM/TSP patients.

HAM/TSP Pathogenesis: The Transmigration Activity of HTLV-1-Infected T Cells into Tissues

“…Thus, activation of small GTPases through both outside-in signaling from integrin and inside-out signaling for integrin in HTLV-1-infected cells of HAM/TSP patients can induce heightened transmigrating activity into the tissues, and these activities might function as one of the first responder roles in the development of HAM/TSP [ 54 ] ( Figure 2 ).…”